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Gene Information

Gene symbol: MLANA

Gene name: melan-A

HGNC ID: 7124

Synonyms: MART1

Related Genes

#	Gene Symbol	Number of hits
1	ACTC1	1 hits
2	ADH1A	1 hits
3	ANKRD36B	1 hits
4	APC	1 hits
5	ARHGEF2	1 hits
6	BCL2	1 hits
7	BCL2L1	1 hits
8	BIRC5	1 hits
9	CCL15	1 hits
10	CCL18	1 hits
11	CCL19	1 hits
12	CCL21	1 hits
13	CCL5	1 hits
14	CCNB1	1 hits
15	CCR5	1 hits
16	CD14	1 hits
17	CD27	1 hits
18	CD274	1 hits
19	CD276	1 hits
20	CD28	1 hits
21	CD34	1 hits
22	CD4	1 hits
23	CD40	1 hits
24	CD40LG	1 hits
25	CD58	1 hits
26	CD63	1 hits
27	CD70	1 hits
28	CD80	1 hits
29	CD83	1 hits
30	CD86	1 hits
31	CD8A	1 hits
32	CEACAM5	1 hits
33	CHL1	1 hits
34	COL1A1	1 hits
35	CSF1	1 hits
36	CSF2	1 hits
37	CTAG1B	1 hits
38	CTNNB1	1 hits
39	CXCL10	1 hits
40	CXCR3	1 hits
41	CYP1B1	1 hits
42	DCT	1 hits
43	DES	1 hits
44	DPEP1	1 hits
45	ERBB2	1 hits
46	FAS	1 hits
47	GFAP	1 hits
48	GSTCD	1 hits
49	GZMB	1 hits
50	HLA-A	1 hits
51	HLA-C	1 hits
52	HLA-DQA1	1 hits
53	HLA-DQB1	1 hits
54	HSPA1A	1 hits
55	ICAM1	1 hits
56	IFNA1	1 hits
57	IFNB1	1 hits
58	IFNG	1 hits
59	IL10	1 hits
60	IL12A	1 hits
61	IL15	1 hits
62	IL17C	1 hits
63	IL1B	1 hits
64	IL2	1 hits
65	IL2RA	1 hits
66	IL3	1 hits
67	IL4	1 hits
68	IL7	1 hits
69	INS	1 hits
70	JAG1	1 hits
71	JUP	1 hits
72	LAG3	1 hits
73	LAMP1	1 hits
74	MAA	1 hits
75	MAGEA1	1 hits
76	MAGEA2	1 hits
77	MAGEA3	1 hits
78	MAGEA4	1 hits
79	MAGEA6	1 hits
80	MBP	1 hits
81	MC1R	1 hits
82	MCAM	1 hits
83	MCO	1 hits
84	MECP2	1 hits
85	MICB	1 hits
86	MITF	1 hits
87	MKI67	1 hits
88	MUC1	1 hits
89	NGFR	1 hits
90	OSM	1 hits
91	PDCD1	1 hits
92	PRAME	1 hits
93	RAB8A	1 hits
94	RANBP2	1 hits
95	S100A1	1 hits
96	SAFB	1 hits
97	SEC14L2	1 hits
98	SEPT4	1 hits
99	SILV	1 hits
100	SOCS1	1 hits
101	SSX2	1 hits
102	TACSTD1	1 hits
103	TFRC	1 hits
104	TLR1	1 hits
105	TLR3	1 hits
106	TLR9	1 hits
107	TNF	1 hits
108	TNFRSF10A	1 hits
109	TP53	1 hits
110	TRNAP1	1 hits
111	TRNAP2	1 hits
112	TYR	1 hits
113	TYRP1	1 hits
114	VHLL	1 hits
115	VIM	1 hits
116	ZFP36	1 hits

Related Sentences

#	PMID	Sentence
1	8543823	Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy.
2	8543823	The human melanoma tumor Ags, MART1 and gp100, are specifically recognized by HLA-A2-restricted CD8+ CTLs derived from melanoma patients and appear to be involved in tumor regression.
3	8543823	Infection of non-Ag expressing HLA-A2+ cell lines A375 and MDA-231 with the vectors resulted in recognition by Ag-specific CTLs as demonstrated by specific target cell lysis and release of cytokines, including IFN-gamma, TNF-alpha, and granulocyte-macrophage-CSF.
4	8543823	Because of the suspected homology between the human MART1 and gp100 genes and their murine counterparts, we immunized C57BL/6 mice with these recombinant adenoviruses and demonstrated that immunization with Ad2CMV-gp100 could protect mice from murine melanoma B16 challenge administered intradermally.
5	8543823	Depletion of CD8+ but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice eliminated the protective effect.
6	8543823	Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy.
7	8543823	The human melanoma tumor Ags, MART1 and gp100, are specifically recognized by HLA-A2-restricted CD8+ CTLs derived from melanoma patients and appear to be involved in tumor regression.
8	8543823	Infection of non-Ag expressing HLA-A2+ cell lines A375 and MDA-231 with the vectors resulted in recognition by Ag-specific CTLs as demonstrated by specific target cell lysis and release of cytokines, including IFN-gamma, TNF-alpha, and granulocyte-macrophage-CSF.
9	8543823	Because of the suspected homology between the human MART1 and gp100 genes and their murine counterparts, we immunized C57BL/6 mice with these recombinant adenoviruses and demonstrated that immunization with Ad2CMV-gp100 could protect mice from murine melanoma B16 challenge administered intradermally.
10	8543823	Depletion of CD8+ but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice eliminated the protective effect.
11	8543823	Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy.
12	8543823	The human melanoma tumor Ags, MART1 and gp100, are specifically recognized by HLA-A2-restricted CD8+ CTLs derived from melanoma patients and appear to be involved in tumor regression.
13	8543823	Infection of non-Ag expressing HLA-A2+ cell lines A375 and MDA-231 with the vectors resulted in recognition by Ag-specific CTLs as demonstrated by specific target cell lysis and release of cytokines, including IFN-gamma, TNF-alpha, and granulocyte-macrophage-CSF.
14	8543823	Because of the suspected homology between the human MART1 and gp100 genes and their murine counterparts, we immunized C57BL/6 mice with these recombinant adenoviruses and demonstrated that immunization with Ad2CMV-gp100 could protect mice from murine melanoma B16 challenge administered intradermally.
15	8543823	Depletion of CD8+ but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice eliminated the protective effect.
16	8587197	In malignant melanoma MAGE-1 and -3 antigen peptides, recognized by specific CTL, were defined.
17	8587197	Tyrosinase, gp100 and Melan A/MART-1, normally expressed in the melanosome, were also shown to be recognized by specific CTL.
18	8587197	These are P1A in mastocytoma P815, MUT1 in murine lung carcinoma (3LL) derived from connexin 37, and pRL1 in murine leukemia RL male 1 derived from c-akt proto-oncogene.
19	8603805	In the present study, we determined the CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase and gp100/Pmel17 in 10 HLA-A2+ melanoma patients and 10 healthy individuals.
20	8603805	Generation of peptide-specific CTL was documented against Melan A/MART-1-derived peptide epitopes, the tyrosinase signal peptide and the influenza matrix peptide after vaccination.
21	8603805	In the present study, we determined the CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase and gp100/Pmel17 in 10 HLA-A2+ melanoma patients and 10 healthy individuals.
22	8603805	Generation of peptide-specific CTL was documented against Melan A/MART-1-derived peptide epitopes, the tyrosinase signal peptide and the influenza matrix peptide after vaccination.
23	8635862	CTL directed against peptides derived from the Melan A/MART-1, tyrosinase and gp100/Pmel17 antigens can be detected in melanoma patients and in healthy controls.
24	8635862	In this study, we examined the expression of Melan A/MART-1, tyrosinase and gp100lPmel17 in fresh melanoma tissues of HLA-A2+ patients and the spontaneous CTL reactivity against antigenic peptides derived from these antigens.
25	8635862	Our results demonstrate an inverse correlation of antigen expression and CTL response to Melan A/MART-1 and tyrosinase in patients with metastatic melanoma.
26	8635862	In 2 patients with advanced disease, CTL responses against Melan A/MART-1 and tyrosinase were induced by intradermal immunization with synthetic nona- or deca-peptides derived from these antigens.
27	8635862	CTL directed against peptides derived from the Melan A/MART-1, tyrosinase and gp100/Pmel17 antigens can be detected in melanoma patients and in healthy controls.
28	8635862	In this study, we examined the expression of Melan A/MART-1, tyrosinase and gp100lPmel17 in fresh melanoma tissues of HLA-A2+ patients and the spontaneous CTL reactivity against antigenic peptides derived from these antigens.
29	8635862	Our results demonstrate an inverse correlation of antigen expression and CTL response to Melan A/MART-1 and tyrosinase in patients with metastatic melanoma.
30	8635862	In 2 patients with advanced disease, CTL responses against Melan A/MART-1 and tyrosinase were induced by intradermal immunization with synthetic nona- or deca-peptides derived from these antigens.
31	8635862	CTL directed against peptides derived from the Melan A/MART-1, tyrosinase and gp100/Pmel17 antigens can be detected in melanoma patients and in healthy controls.
32	8635862	In this study, we examined the expression of Melan A/MART-1, tyrosinase and gp100lPmel17 in fresh melanoma tissues of HLA-A2+ patients and the spontaneous CTL reactivity against antigenic peptides derived from these antigens.
33	8635862	Our results demonstrate an inverse correlation of antigen expression and CTL response to Melan A/MART-1 and tyrosinase in patients with metastatic melanoma.
34	8635862	In 2 patients with advanced disease, CTL responses against Melan A/MART-1 and tyrosinase were induced by intradermal immunization with synthetic nona- or deca-peptides derived from these antigens.
35	8635862	CTL directed against peptides derived from the Melan A/MART-1, tyrosinase and gp100/Pmel17 antigens can be detected in melanoma patients and in healthy controls.
36	8635862	In this study, we examined the expression of Melan A/MART-1, tyrosinase and gp100lPmel17 in fresh melanoma tissues of HLA-A2+ patients and the spontaneous CTL reactivity against antigenic peptides derived from these antigens.
37	8635862	Our results demonstrate an inverse correlation of antigen expression and CTL response to Melan A/MART-1 and tyrosinase in patients with metastatic melanoma.
38	8635862	In 2 patients with advanced disease, CTL responses against Melan A/MART-1 and tyrosinase were induced by intradermal immunization with synthetic nona- or deca-peptides derived from these antigens.
39	8640065	Such antigens include MAGE-1, MAGE-3, MART-1/Melan-A, gp100, tyrosinase, the tyrosinase-related antigen gp75, the antigen gp15 and the mutated CDK4 and beta-catenin gene-products.
40	8640065	This should include examination of melanoma antigen and MHC class I allele expression in the individual patient's tumour, assessment of the status of the peptide transporter molecules TAP1/TAP2 and evaluation of T-cell mediated immune responses reactive against peptides and autologous melanoma.
41	8690525	Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo.
42	8690525	In the present study, we determined CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase, and gp100/Pmel17 in 3 HLA-A2+ melanoma patients.
43	8690525	Enhanced DTH reactions and CD8+ CTL responses were observed after treatment with systemic GM-CSF.
44	8690525	Immunohistochemical characterization of DTH-constituting elements revealed infiltrates of CD4+ and CD8+ T lymphocytes and strong expression of IL-2 and gammaIFN, suggesting the activation of CD4+ ThI and CD8+ CTL by peptides presented by MHC-class-I molecules of dermal APC.
45	8811494	Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.
46	8811494	MART-1 and gp100 melanoma associated antigens (MAA) are expressed by cells of the melanocytic lineage and are recognized by the majority of HLA-A2 restricted tumor-infiltrating lymphocytes.
47	8811494	One cell line did not express MART-1 or gp100.
48	8811494	None of the nonmelanoma cancer lines tested stained for MART-1 or gp100.
49	8811494	Analysis of melanoma lesions by immunohistochemistry showed significant heterogeneity of expression of both MART-1 and gp100 MAA either as a percentage of cells expressing MAA or as intensity of expression.
50	8811494	Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.
51	8811494	MART-1 and gp100 melanoma associated antigens (MAA) are expressed by cells of the melanocytic lineage and are recognized by the majority of HLA-A2 restricted tumor-infiltrating lymphocytes.
52	8811494	One cell line did not express MART-1 or gp100.
53	8811494	None of the nonmelanoma cancer lines tested stained for MART-1 or gp100.
54	8811494	Analysis of melanoma lesions by immunohistochemistry showed significant heterogeneity of expression of both MART-1 and gp100 MAA either as a percentage of cells expressing MAA or as intensity of expression.
55	8811494	Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.
56	8811494	MART-1 and gp100 melanoma associated antigens (MAA) are expressed by cells of the melanocytic lineage and are recognized by the majority of HLA-A2 restricted tumor-infiltrating lymphocytes.
57	8811494	One cell line did not express MART-1 or gp100.
58	8811494	None of the nonmelanoma cancer lines tested stained for MART-1 or gp100.
59	8811494	Analysis of melanoma lesions by immunohistochemistry showed significant heterogeneity of expression of both MART-1 and gp100 MAA either as a percentage of cells expressing MAA or as intensity of expression.
60	8811494	Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.
61	8811494	MART-1 and gp100 melanoma associated antigens (MAA) are expressed by cells of the melanocytic lineage and are recognized by the majority of HLA-A2 restricted tumor-infiltrating lymphocytes.
62	8811494	One cell line did not express MART-1 or gp100.
63	8811494	None of the nonmelanoma cancer lines tested stained for MART-1 or gp100.
64	8811494	Analysis of melanoma lesions by immunohistochemistry showed significant heterogeneity of expression of both MART-1 and gp100 MAA either as a percentage of cells expressing MAA or as intensity of expression.
65	8811494	Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.
66	8811494	MART-1 and gp100 melanoma associated antigens (MAA) are expressed by cells of the melanocytic lineage and are recognized by the majority of HLA-A2 restricted tumor-infiltrating lymphocytes.
67	8811494	One cell line did not express MART-1 or gp100.
68	8811494	None of the nonmelanoma cancer lines tested stained for MART-1 or gp100.
69	8811494	Analysis of melanoma lesions by immunohistochemistry showed significant heterogeneity of expression of both MART-1 and gp100 MAA either as a percentage of cells expressing MAA or as intensity of expression.
70	8938270	MAGE, tyrosinase, melan-A and gp75) and mutant oncogene products (e.g. p53, ras, and HER-2/neu).
71	9101410	Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100.
72	9101410	To develop a syngeneic animal model for evaluating antigen-specific vaccines in cancer therapy, the murine homologues of the human melanoma antigens MART1 and gp100, which were specifically recognized by tumor-infiltrating lymphocytes from patients with melanoma, were cloned and sequenced from a murine B16 melanoma cDNA library.
73	9101410	The open reading frames of murine MART1 and gp100 encode proteins of 113- and 626-amino acids with 68.8 and 77% identity to the respective human proteins.
74	9101410	Mice immunized with murine MART1 or gp100 using recombinant vaccinia virus failed to produce any detectable T-cell responses or protective immunity against B16 melanoma.
75	9101410	Immunization with human and mouse gp100 together [adenovirus type 2 (Ad2)-hgp100 plus recombinant vaccinia virus (rVV)-mgp100], or immunization with human gp100 (Ad2-hgp100) and boosting with heterologous vector (rVV-hgp100 or rVV-mgp100) or homologous vector (Ad2-hgp100), did not significantly enhance the protective response against B16 melanoma.
76	9101410	Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100.
77	9101410	To develop a syngeneic animal model for evaluating antigen-specific vaccines in cancer therapy, the murine homologues of the human melanoma antigens MART1 and gp100, which were specifically recognized by tumor-infiltrating lymphocytes from patients with melanoma, were cloned and sequenced from a murine B16 melanoma cDNA library.
78	9101410	The open reading frames of murine MART1 and gp100 encode proteins of 113- and 626-amino acids with 68.8 and 77% identity to the respective human proteins.
79	9101410	Mice immunized with murine MART1 or gp100 using recombinant vaccinia virus failed to produce any detectable T-cell responses or protective immunity against B16 melanoma.
80	9101410	Immunization with human and mouse gp100 together [adenovirus type 2 (Ad2)-hgp100 plus recombinant vaccinia virus (rVV)-mgp100], or immunization with human gp100 (Ad2-hgp100) and boosting with heterologous vector (rVV-hgp100 or rVV-mgp100) or homologous vector (Ad2-hgp100), did not significantly enhance the protective response against B16 melanoma.
81	9101410	Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100.
82	9101410	To develop a syngeneic animal model for evaluating antigen-specific vaccines in cancer therapy, the murine homologues of the human melanoma antigens MART1 and gp100, which were specifically recognized by tumor-infiltrating lymphocytes from patients with melanoma, were cloned and sequenced from a murine B16 melanoma cDNA library.
83	9101410	The open reading frames of murine MART1 and gp100 encode proteins of 113- and 626-amino acids with 68.8 and 77% identity to the respective human proteins.
84	9101410	Mice immunized with murine MART1 or gp100 using recombinant vaccinia virus failed to produce any detectable T-cell responses or protective immunity against B16 melanoma.
85	9101410	Immunization with human and mouse gp100 together [adenovirus type 2 (Ad2)-hgp100 plus recombinant vaccinia virus (rVV)-mgp100], or immunization with human gp100 (Ad2-hgp100) and boosting with heterologous vector (rVV-hgp100 or rVV-mgp100) or homologous vector (Ad2-hgp100), did not significantly enhance the protective response against B16 melanoma.
86	9101410	Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100.
87	9101410	To develop a syngeneic animal model for evaluating antigen-specific vaccines in cancer therapy, the murine homologues of the human melanoma antigens MART1 and gp100, which were specifically recognized by tumor-infiltrating lymphocytes from patients with melanoma, were cloned and sequenced from a murine B16 melanoma cDNA library.
88	9101410	The open reading frames of murine MART1 and gp100 encode proteins of 113- and 626-amino acids with 68.8 and 77% identity to the respective human proteins.
89	9101410	Mice immunized with murine MART1 or gp100 using recombinant vaccinia virus failed to produce any detectable T-cell responses or protective immunity against B16 melanoma.
90	9101410	Immunization with human and mouse gp100 together [adenovirus type 2 (Ad2)-hgp100 plus recombinant vaccinia virus (rVV)-mgp100], or immunization with human gp100 (Ad2-hgp100) and boosting with heterologous vector (rVV-hgp100 or rVV-mgp100) or homologous vector (Ad2-hgp100), did not significantly enhance the protective response against B16 melanoma.
91	9131386	Immunobiology of human melanoma antigens MART-1 and gp100 and their use for immuno-gene therapy.
92	9131386	Two genes encoding human melanoma antigens MART-1 and gp100 recognized by HLA-A2 restricted melanoma reactive CTL derived from tumor infiltrating lymphocytes (TIL) were isolated by cDNA expression cloning methods.
93	9131386	Immunobiology of human melanoma antigens MART-1 and gp100 and their use for immuno-gene therapy.
94	9131386	Two genes encoding human melanoma antigens MART-1 and gp100 recognized by HLA-A2 restricted melanoma reactive CTL derived from tumor infiltrating lymphocytes (TIL) were isolated by cDNA expression cloning methods.
95	9139889	The capacity of rVV-M to generate HLA-A2.1-restricted MART-1/Melan A-specific CTL was demonstrated from tumor-infiltrating-lymphocyte (TIL) cultures and from healthy donors' peripheral-blood mononuclear cells (PBMC).
96	9139889	MART-1/Melan-A27-35-specific CTL were generated from TIL after 2 weekly stimulation courses.
97	9139889	In addition, TNF-alpha production could be induced in rVV-M-stimulated CTL upon co-culture with COS-7 cells transiently transfected with MART-1/Melan-A and HLA-A2.1 genes.
98	9139889	The capacity of rVV-M to generate HLA-A2.1-restricted MART-1/Melan A-specific CTL was demonstrated from tumor-infiltrating-lymphocyte (TIL) cultures and from healthy donors' peripheral-blood mononuclear cells (PBMC).
99	9139889	MART-1/Melan-A27-35-specific CTL were generated from TIL after 2 weekly stimulation courses.
100	9139889	In addition, TNF-alpha production could be induced in rVV-M-stimulated CTL upon co-culture with COS-7 cells transiently transfected with MART-1/Melan-A and HLA-A2.1 genes.
101	9139889	The capacity of rVV-M to generate HLA-A2.1-restricted MART-1/Melan A-specific CTL was demonstrated from tumor-infiltrating-lymphocyte (TIL) cultures and from healthy donors' peripheral-blood mononuclear cells (PBMC).
102	9139889	MART-1/Melan-A27-35-specific CTL were generated from TIL after 2 weekly stimulation courses.
103	9139889	In addition, TNF-alpha production could be induced in rVV-M-stimulated CTL upon co-culture with COS-7 cells transiently transfected with MART-1/Melan-A and HLA-A2.1 genes.
104	9220317	In 6/6 HLA A*0201-expressing melanoma patients tested, the virally driven expression of MART-1/Melan A MAA by DC was sufficient to generate CD8+ T lymphocytes that could recognize naturally processed epitopes on tumor cells.
105	9336741	We have transfected human melanoma cell line 518A2 with the cDNA encoding interleukin-2 (IL-2) or granulocyte-macrophage colony-stimulating factor (GM-CSF), and compared cytokine-producing clones for their ability to induce melanoma-specific cytotoxic T lymphocytes (CTL) from autologous peripheral blood mononuclear cells (PBMC) in vitro.
106	9336741	The parental cell line expressed HLA-A1, HLA-A2, ICAM-1, LFA-3, in addition to the common CTL antigens MAGE-1, MAGE-3, tyrosinase, gp100, and Melan-A/MART-1.
107	9378560	Stimulation of CD8+ T cell responses to MAGE-3 and Melan A/MART-1 by immunization to a polyvalent melanoma vaccine.
108	9378560	In this study, we tested the ability of a polyvalent melanoma vaccine to induce CD8+ T cell responses to the melanoma associated antigens MAGE-3 and Melan A/MART-1.
109	9378560	CD8+ T cells in peripheral blood reacting to HLA-A2 restricted epitopes on MAGE-3 (FLWGPRALV) and Melan A/MART-1/(AAGIGILTV) were quantitated using a filter spot assay at baseline and following 4 immunizations.
110	9378560	Our results demonstrate directly that MAGE-3 and Melan A/MART-1 can stimulate CD8+ T cell responses in humans, and suggest that these responses are protective and surrogate markers of vaccine efficacy.
111	9378560	Stimulation of CD8+ T cell responses to MAGE-3 and Melan A/MART-1 by immunization to a polyvalent melanoma vaccine.
112	9378560	In this study, we tested the ability of a polyvalent melanoma vaccine to induce CD8+ T cell responses to the melanoma associated antigens MAGE-3 and Melan A/MART-1.
113	9378560	CD8+ T cells in peripheral blood reacting to HLA-A2 restricted epitopes on MAGE-3 (FLWGPRALV) and Melan A/MART-1/(AAGIGILTV) were quantitated using a filter spot assay at baseline and following 4 immunizations.
114	9378560	Our results demonstrate directly that MAGE-3 and Melan A/MART-1 can stimulate CD8+ T cell responses in humans, and suggest that these responses are protective and surrogate markers of vaccine efficacy.
115	9378560	Stimulation of CD8+ T cell responses to MAGE-3 and Melan A/MART-1 by immunization to a polyvalent melanoma vaccine.
116	9378560	In this study, we tested the ability of a polyvalent melanoma vaccine to induce CD8+ T cell responses to the melanoma associated antigens MAGE-3 and Melan A/MART-1.
117	9378560	CD8+ T cells in peripheral blood reacting to HLA-A2 restricted epitopes on MAGE-3 (FLWGPRALV) and Melan A/MART-1/(AAGIGILTV) were quantitated using a filter spot assay at baseline and following 4 immunizations.
118	9378560	Our results demonstrate directly that MAGE-3 and Melan A/MART-1 can stimulate CD8+ T cell responses in humans, and suggest that these responses are protective and surrogate markers of vaccine efficacy.
119	9378560	Stimulation of CD8+ T cell responses to MAGE-3 and Melan A/MART-1 by immunization to a polyvalent melanoma vaccine.
120	9378560	In this study, we tested the ability of a polyvalent melanoma vaccine to induce CD8+ T cell responses to the melanoma associated antigens MAGE-3 and Melan A/MART-1.
121	9378560	CD8+ T cells in peripheral blood reacting to HLA-A2 restricted epitopes on MAGE-3 (FLWGPRALV) and Melan A/MART-1/(AAGIGILTV) were quantitated using a filter spot assay at baseline and following 4 immunizations.
122	9378560	Our results demonstrate directly that MAGE-3 and Melan A/MART-1 can stimulate CD8+ T cell responses in humans, and suggest that these responses are protective and surrogate markers of vaccine efficacy.
123	9396616	Pmel 17 and Melan A have led to vaccines developed against differentiation antigens expressed in other solid tumors.
124	9396616	Similarly HER2/neu and mucin overexpression in breast cancer represent promising targets.
125	9469433	HLA-A*0201-restricted Melan-A-specific CTL recognize primarily the Melan-A(27-35) (AAGIGILTV) and the Melan-A(26-35) (EAAGIGILTV) peptides.
126	9469433	Surprisingly, analogues of the Melan-A(27-35) peptide, which bound more efficiently than the natural nonapeptide to HLA-A*0201, were poorly recognized by tumor-reactive CTL.
127	9469433	These results suggest that the Melan-A(26-35) peptide analogue ELAGIGILTV may be more immunogenic than the natural peptides in HLA-A*0201 melanoma patients and should thus be considered as a candidate for future peptide-based vaccine trials.
128	9469433	HLA-A*0201-restricted Melan-A-specific CTL recognize primarily the Melan-A(27-35) (AAGIGILTV) and the Melan-A(26-35) (EAAGIGILTV) peptides.
129	9469433	Surprisingly, analogues of the Melan-A(27-35) peptide, which bound more efficiently than the natural nonapeptide to HLA-A*0201, were poorly recognized by tumor-reactive CTL.
130	9469433	These results suggest that the Melan-A(26-35) peptide analogue ELAGIGILTV may be more immunogenic than the natural peptides in HLA-A*0201 melanoma patients and should thus be considered as a candidate for future peptide-based vaccine trials.
131	9469433	HLA-A*0201-restricted Melan-A-specific CTL recognize primarily the Melan-A(27-35) (AAGIGILTV) and the Melan-A(26-35) (EAAGIGILTV) peptides.
132	9469433	Surprisingly, analogues of the Melan-A(27-35) peptide, which bound more efficiently than the natural nonapeptide to HLA-A*0201, were poorly recognized by tumor-reactive CTL.
133	9469433	These results suggest that the Melan-A(26-35) peptide analogue ELAGIGILTV may be more immunogenic than the natural peptides in HLA-A*0201 melanoma patients and should thus be considered as a candidate for future peptide-based vaccine trials.
134	9498746	To identify shared epitopes for melanoma-reactive CTL restricted by MHC molecules other than HLA-A*0201, six human melanoma patient CTL lines expressing HLA-A1 were screened for reactivity against the melanocyte differentiation proteins Pmel-17/gp100, MART-1/Melan-A, and tyrosinase, expressed via recombinant vaccinia virus vectors.
135	9551367	We have evaluated the abilities of a series of defined synthetic peptide epitopes derived from MART-1/Melan-A, gp100, tyrosinase, and MAGE-3 or unfractionated peptides naturally presented by melanoma MHC molecules to elicit HLA-A2-restricted and melanoma-reactive CTLs from the peripheral blood of normal donors or patients with metastatic melanoma.
136	9551367	Autologous peripheral blood dendritic cells (DCs), which were easily generated from all donors when cultured in the presence of recombinant human interleukin-4 and recombinant human granulocyte-macrophage colony-stimulating factor were pulsed with melanoma peptides and used to "prime" and/or "boost" CTL cultures in vitro.
137	9551367	Our results suggest that antimelanoma CTLs may be reproducibly generated in short-term in vitro cultures in this manner using either a subset of the defined synthetic peptides (MART-1/Melan-A27-35, MART-1/Melan-A32-40, gp100(280-288), tyrosinase368-376, and MAGE-3(271-279)) or unfractionated peptides (containing both idiotypic and shared melanoma epitopes) derived from freshly isolated autologous melanoma lesions.
138	9551367	We have evaluated the abilities of a series of defined synthetic peptide epitopes derived from MART-1/Melan-A, gp100, tyrosinase, and MAGE-3 or unfractionated peptides naturally presented by melanoma MHC molecules to elicit HLA-A2-restricted and melanoma-reactive CTLs from the peripheral blood of normal donors or patients with metastatic melanoma.
139	9551367	Autologous peripheral blood dendritic cells (DCs), which were easily generated from all donors when cultured in the presence of recombinant human interleukin-4 and recombinant human granulocyte-macrophage colony-stimulating factor were pulsed with melanoma peptides and used to "prime" and/or "boost" CTL cultures in vitro.
140	9551367	Our results suggest that antimelanoma CTLs may be reproducibly generated in short-term in vitro cultures in this manner using either a subset of the defined synthetic peptides (MART-1/Melan-A27-35, MART-1/Melan-A32-40, gp100(280-288), tyrosinase368-376, and MAGE-3(271-279)) or unfractionated peptides (containing both idiotypic and shared melanoma epitopes) derived from freshly isolated autologous melanoma lesions.
141	9570527	Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the Th1-biasing cytokines IL-12 and IFN-alpha.
142	9570527	Cultured, monocyte-derived dendritic cells (DC) were transiently transfected with plasmid DNA encoding human MART-1/Melan-A, pMel-17/gp100, tyrosinase, MAGE-1, or MAGE-3 by particle bombardment and used to stimulate autologous PBMC responder T cells.
143	9570527	Coinsertion of genes encoding the Th1-biasing cytokines IL-12 or IFN-alpha consistently enhanced the magnitude of the resulting Ag-specific CTL reactivity.
144	9692858	To establish a mouse model for the use of these 'self' antigens as targets for anti-tumor immune responses, we have employed the mouse homologues of the human melanoma antigens Tyrosinase, Tyrosinase Related Protein-1 (TRP-1), gp100, and MART-1.
145	9692858	The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16.
146	9692858	Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues.
147	9692858	Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens.
148	9692858	To establish a mouse model for the use of these 'self' antigens as targets for anti-tumor immune responses, we have employed the mouse homologues of the human melanoma antigens Tyrosinase, Tyrosinase Related Protein-1 (TRP-1), gp100, and MART-1.
149	9692858	The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16.
150	9692858	Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues.
151	9692858	Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens.
152	9692858	To establish a mouse model for the use of these 'self' antigens as targets for anti-tumor immune responses, we have employed the mouse homologues of the human melanoma antigens Tyrosinase, Tyrosinase Related Protein-1 (TRP-1), gp100, and MART-1.
153	9692858	The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16.
154	9692858	Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues.
155	9692858	Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens.
156	9815761	Granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 microgram) and MART-1(27-35) peptide (128 microgram in DMSO) were formulated into p-GlcNAc.
157	9815761	Peptide release was assayed in vitro using interleukin 2 production from previously characterized MART-1(27-35)-specific Jurkat T cells (JRT22).
158	9815761	Granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 microgram) and MART-1(27-35) peptide (128 microgram in DMSO) were formulated into p-GlcNAc.
159	9815761	Peptide release was assayed in vitro using interleukin 2 production from previously characterized MART-1(27-35)-specific Jurkat T cells (JRT22).
160	9816214	Specific CD8(+) CTL recognition of melanoma requires expression of MHC class I molecules as well as melanoma-associated peptide epitopes.
161	9816214	Stable MHC class I cell surface expression requires delivery of cytosolic peptides into the endoplasmic reticulum by the peptide transporter molecules TAP1 and TAP2, with peptides subsequently transported to the cell surface in complexes containing MHC class I heavy chain and beta2-microglobulin.
162	9816214	We have evaluated a series of mechanisms resulting in MHC class I down-regulation in a human melanoma cell line, Mz18, typed as HLA-A2(+), A3(+), B7(+), B57(+), Cw1(+), and Cw6(+) by genomic PCR analysis.
163	9816214	The melanoma cell line Mz18 exhibits a global down-regulation of MHC class I heavy chain transcripts; beta2-microglobulin; the proteasome subunits LMP2/7, involved in generating cytosolic peptide fragments; and the peptide transporter molecules TAP1 and TAP2, involved in peptide transport from the cytosol into the endoplasmic reticulum.
164	9816214	IFN-gamma treatment of Mz18 melanoma cells leads to up-regulation of LMP2/7 and TAP1/2, as well as to up-regulation of HLA-B and HLA-C MHC loci alleles, but not HLA-A2 or HLA-A3.
165	9816214	Melanoma peptides could only be presented and recognized by CTLs if the HLA-A2-transfected Mz18 cell line was first treated with IFN-gamma, thereby restoring LMP2/7 and TAP1/2 expression and function.
166	9816214	Because several melanoma antigens recognized by T cells have been reported to be presented by HLA-A2 (MART-1/Melan-A, tyrosinase, gp100, and MAGE-3), the loss of HLA-A2 molecules may represent an important mechanism by which many melanomas evade immune recognition.
167	9816214	These findings suggest that patients entering clinical trials for immunotherapy with melanoma vaccines should be carefully examined for tumor cell allelic MHC class I loss and whether such MHC class I antigen down-regulation can be restored by cytokines.
168	9850054	Generation of CD8+ and CD4+ T-cell response to dendritic cells genetically engineered to express the MART-1/Melan-A gene.
169	9850054	Both CD8+ and CD4+ T cells have demonstrated roles in antitumor immune response in many animal tumor systems.
170	9850054	In many human tumor systems, although abundant literature exists on the evidence of tumor antigen-specific CD8+ CTL response, only limited information is available on tumor antigen-specific CD4+ T-cell response.
171	9850054	Using the MART-1/Melan-A (MART-1) antigen system as a prototype human tumor-associated antigen (TAA)- and dendritic cell (DC)-based MART-1 antigen presentation system (i.e., DCs transduced with an adenoviral vector-based construct carrying the MART-1 gene), we explored, in vitro, the feasibility of generating both CD8+ and CD4+ T-cell responses in the same individual.
172	9850054	Here, we show that autologous DCs from both HLA-A2-positive melanoma patients and normal healthy individuals that are transduced with an adenoviral vector containing the MART-1 antigen are capable of inducing both MART-1-specific CD8+ and CD4+ T cells in in vitro coculture.
173	9850054	After several rounds of stimulation, both the CD4+ and CD8+ T cells synthesized IFN-gamma when they were specifically stimulated.
174	9850054	The CD8+ T cells generated in such cocultures also recognized the MART-1(27-35) peptide, AAGIGILTV, in 4-h cytotoxicity assays.
175	9850054	Generation of CD8+ and CD4+ T-cell response to dendritic cells genetically engineered to express the MART-1/Melan-A gene.
176	9850054	Both CD8+ and CD4+ T cells have demonstrated roles in antitumor immune response in many animal tumor systems.
177	9850054	In many human tumor systems, although abundant literature exists on the evidence of tumor antigen-specific CD8+ CTL response, only limited information is available on tumor antigen-specific CD4+ T-cell response.
178	9850054	Using the MART-1/Melan-A (MART-1) antigen system as a prototype human tumor-associated antigen (TAA)- and dendritic cell (DC)-based MART-1 antigen presentation system (i.e., DCs transduced with an adenoviral vector-based construct carrying the MART-1 gene), we explored, in vitro, the feasibility of generating both CD8+ and CD4+ T-cell responses in the same individual.
179	9850054	Here, we show that autologous DCs from both HLA-A2-positive melanoma patients and normal healthy individuals that are transduced with an adenoviral vector containing the MART-1 antigen are capable of inducing both MART-1-specific CD8+ and CD4+ T cells in in vitro coculture.
180	9850054	After several rounds of stimulation, both the CD4+ and CD8+ T cells synthesized IFN-gamma when they were specifically stimulated.
181	9850054	The CD8+ T cells generated in such cocultures also recognized the MART-1(27-35) peptide, AAGIGILTV, in 4-h cytotoxicity assays.
182	9850054	Generation of CD8+ and CD4+ T-cell response to dendritic cells genetically engineered to express the MART-1/Melan-A gene.
183	9850054	Both CD8+ and CD4+ T cells have demonstrated roles in antitumor immune response in many animal tumor systems.
184	9850054	In many human tumor systems, although abundant literature exists on the evidence of tumor antigen-specific CD8+ CTL response, only limited information is available on tumor antigen-specific CD4+ T-cell response.
185	9850054	Using the MART-1/Melan-A (MART-1) antigen system as a prototype human tumor-associated antigen (TAA)- and dendritic cell (DC)-based MART-1 antigen presentation system (i.e., DCs transduced with an adenoviral vector-based construct carrying the MART-1 gene), we explored, in vitro, the feasibility of generating both CD8+ and CD4+ T-cell responses in the same individual.
186	9850054	Here, we show that autologous DCs from both HLA-A2-positive melanoma patients and normal healthy individuals that are transduced with an adenoviral vector containing the MART-1 antigen are capable of inducing both MART-1-specific CD8+ and CD4+ T cells in in vitro coculture.
187	9850054	After several rounds of stimulation, both the CD4+ and CD8+ T cells synthesized IFN-gamma when they were specifically stimulated.
188	9850054	The CD8+ T cells generated in such cocultures also recognized the MART-1(27-35) peptide, AAGIGILTV, in 4-h cytotoxicity assays.
189	9850054	Generation of CD8+ and CD4+ T-cell response to dendritic cells genetically engineered to express the MART-1/Melan-A gene.
190	9850054	Both CD8+ and CD4+ T cells have demonstrated roles in antitumor immune response in many animal tumor systems.
191	9850054	In many human tumor systems, although abundant literature exists on the evidence of tumor antigen-specific CD8+ CTL response, only limited information is available on tumor antigen-specific CD4+ T-cell response.
192	9850054	Using the MART-1/Melan-A (MART-1) antigen system as a prototype human tumor-associated antigen (TAA)- and dendritic cell (DC)-based MART-1 antigen presentation system (i.e., DCs transduced with an adenoviral vector-based construct carrying the MART-1 gene), we explored, in vitro, the feasibility of generating both CD8+ and CD4+ T-cell responses in the same individual.
193	9850054	Here, we show that autologous DCs from both HLA-A2-positive melanoma patients and normal healthy individuals that are transduced with an adenoviral vector containing the MART-1 antigen are capable of inducing both MART-1-specific CD8+ and CD4+ T cells in in vitro coculture.
194	9850054	After several rounds of stimulation, both the CD4+ and CD8+ T cells synthesized IFN-gamma when they were specifically stimulated.
195	9850054	The CD8+ T cells generated in such cocultures also recognized the MART-1(27-35) peptide, AAGIGILTV, in 4-h cytotoxicity assays.
196	9862627	Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens.
197	9862730	Diversity of the fine specificity displayed by HLA-A*0201-restricted CTL specific for the immunodominant Melan-A/MART-1 antigenic peptide.
198	9862730	HLA-A*0201 melanoma patients often develop a CTL response to an immunodominant peptide derived from the melanocyte lineage-specific protein Melan-A/MART-1.
199	9862730	To substantiate this observation, we have now tested a series of Melan-A(26-35) variant peptides containing single alanine substitutions for binding to HLA-A*0201 and recognition by polyclonal and monoclonal Melan-A-specific CTL.
200	9862730	Diversity of the fine specificity displayed by HLA-A*0201-restricted CTL specific for the immunodominant Melan-A/MART-1 antigenic peptide.
201	9862730	HLA-A*0201 melanoma patients often develop a CTL response to an immunodominant peptide derived from the melanocyte lineage-specific protein Melan-A/MART-1.
202	9862730	To substantiate this observation, we have now tested a series of Melan-A(26-35) variant peptides containing single alanine substitutions for binding to HLA-A*0201 and recognition by polyclonal and monoclonal Melan-A-specific CTL.
203	9862730	Diversity of the fine specificity displayed by HLA-A*0201-restricted CTL specific for the immunodominant Melan-A/MART-1 antigenic peptide.
204	9862730	HLA-A*0201 melanoma patients often develop a CTL response to an immunodominant peptide derived from the melanocyte lineage-specific protein Melan-A/MART-1.
205	9862730	To substantiate this observation, we have now tested a series of Melan-A(26-35) variant peptides containing single alanine substitutions for binding to HLA-A*0201 and recognition by polyclonal and monoclonal Melan-A-specific CTL.
206	9862732	HLA-independent heterogeneity of CD8+ T cell responses to MAGE-3, Melan-A/MART-1, gp100, tyrosinase, MC1R, and TRP-2 in vaccine-treated melanoma patients.
207	9862732	To identify such peptides, we evaluated HLA-A*02+ melanoma patients immunized to a polyvalent vaccine containing multiple Ags, including MAGE-3, Melan-A/MART-1, gp100, tyrosinase, melanocortin receptor (MC1R), and dopachrome tautomerase (TRP-2).
208	9862732	Using a filter spot assay, we measured peripheral blood CD8+ T cell responses, before and after immunization, to a panel of 45 HLA-A*0201-restricted peptides derived from these Ags.
209	9862732	HLA-independent heterogeneity of CD8+ T cell responses to MAGE-3, Melan-A/MART-1, gp100, tyrosinase, MC1R, and TRP-2 in vaccine-treated melanoma patients.
210	9862732	To identify such peptides, we evaluated HLA-A*02+ melanoma patients immunized to a polyvalent vaccine containing multiple Ags, including MAGE-3, Melan-A/MART-1, gp100, tyrosinase, melanocortin receptor (MC1R), and dopachrome tautomerase (TRP-2).
211	9862732	Using a filter spot assay, we measured peripheral blood CD8+ T cell responses, before and after immunization, to a panel of 45 HLA-A*0201-restricted peptides derived from these Ags.
212	10077623	When we tried to induce immune responses to five mouse melanocyte differentiation antigens, gp100, MART-1, tyrosinase, and tyrosinase-related proteins (TRP) 1 and TRP-2, we observed striking depigmentation and melanocyte destruction only in the skin of mice inoculated with a vaccinia virus encoding mouse TRP-1.
213	10092815	Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice.
214	10092815	Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes.
215	10092815	In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice.
216	10092815	More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner.
217	10092815	Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
218	10092815	Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice.
219	10092815	Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes.
220	10092815	In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice.
221	10092815	More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner.
222	10092815	Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
223	10092815	Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice.
224	10092815	Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes.
225	10092815	In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice.
226	10092815	More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner.
227	10092815	Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
228	10092815	Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice.
229	10092815	Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes.
230	10092815	In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice.
231	10092815	More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner.
232	10092815	Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
233	10092815	Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice.
234	10092815	Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes.
235	10092815	In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice.
236	10092815	More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner.
237	10092815	Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
238	10388061	Melanoma serves as a paradigm of an immunogenic human tumor, and several tumor antigens, including MAGE, MART-1/Melan-A and gp100, recognized by CTLs, have now been isolated.
239	10388087	Instead, new vaccines like MART-1, gp100, p53 and ras peptides are targeting the cancer cell's ability to evade immune surveillance.
240	10417764	Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
241	10417764	Melanoma-reactive human cytotoxic T lymphocytes (CTLs) mediate tumor regression in vivo through specific recognition of MHC-associated peptide epitopes, many of which are encoded by the melanocytic tissue differentiation proteins gp100/Pme117 and MART-1/Melan-A.
242	10417764	Especially where these peptides may be used in human clinical trials for the treatment or prevention of cancer, there is substantial need for direct evaluation of HLA-A*0201-associated peptides from MART-1 and gp100 that are naturally processed and presented.
243	10417764	To that end, we have isolated peptides directly from HLA-A*0201 molecules of human melanoma cells and have determined that naturally processed epitopes for HLA-A*0201-restricted, melanoma-reactive CTLs include the nonamers MART-1(27-35) (AAGIGILTV), gp100(154-162) (KTWGQYWQV), gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA) and the decamer gp100(476-485) (VLYRYGSFSV).
244	10417764	HLA-A*0201-restricted CTLs from one melanoma patient who has survived metastatic disease recognized MART-1(27-35) (AAGIGILTV), gp100(280-288) (YLEPGPVTA) and gp100(154-162) (KTWGQYWQV) and were cross-reactive on longer peptides that contained these nonamer sequences.
245	10417764	Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
246	10417764	Melanoma-reactive human cytotoxic T lymphocytes (CTLs) mediate tumor regression in vivo through specific recognition of MHC-associated peptide epitopes, many of which are encoded by the melanocytic tissue differentiation proteins gp100/Pme117 and MART-1/Melan-A.
247	10417764	Especially where these peptides may be used in human clinical trials for the treatment or prevention of cancer, there is substantial need for direct evaluation of HLA-A*0201-associated peptides from MART-1 and gp100 that are naturally processed and presented.
248	10417764	To that end, we have isolated peptides directly from HLA-A*0201 molecules of human melanoma cells and have determined that naturally processed epitopes for HLA-A*0201-restricted, melanoma-reactive CTLs include the nonamers MART-1(27-35) (AAGIGILTV), gp100(154-162) (KTWGQYWQV), gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA) and the decamer gp100(476-485) (VLYRYGSFSV).
249	10417764	HLA-A*0201-restricted CTLs from one melanoma patient who has survived metastatic disease recognized MART-1(27-35) (AAGIGILTV), gp100(280-288) (YLEPGPVTA) and gp100(154-162) (KTWGQYWQV) and were cross-reactive on longer peptides that contained these nonamer sequences.
250	10417764	Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
251	10417764	Melanoma-reactive human cytotoxic T lymphocytes (CTLs) mediate tumor regression in vivo through specific recognition of MHC-associated peptide epitopes, many of which are encoded by the melanocytic tissue differentiation proteins gp100/Pme117 and MART-1/Melan-A.
252	10417764	Especially where these peptides may be used in human clinical trials for the treatment or prevention of cancer, there is substantial need for direct evaluation of HLA-A*0201-associated peptides from MART-1 and gp100 that are naturally processed and presented.
253	10417764	To that end, we have isolated peptides directly from HLA-A*0201 molecules of human melanoma cells and have determined that naturally processed epitopes for HLA-A*0201-restricted, melanoma-reactive CTLs include the nonamers MART-1(27-35) (AAGIGILTV), gp100(154-162) (KTWGQYWQV), gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA) and the decamer gp100(476-485) (VLYRYGSFSV).
254	10417764	HLA-A*0201-restricted CTLs from one melanoma patient who has survived metastatic disease recognized MART-1(27-35) (AAGIGILTV), gp100(280-288) (YLEPGPVTA) and gp100(154-162) (KTWGQYWQV) and were cross-reactive on longer peptides that contained these nonamer sequences.
255	10417764	Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
256	10417764	Melanoma-reactive human cytotoxic T lymphocytes (CTLs) mediate tumor regression in vivo through specific recognition of MHC-associated peptide epitopes, many of which are encoded by the melanocytic tissue differentiation proteins gp100/Pme117 and MART-1/Melan-A.
257	10417764	Especially where these peptides may be used in human clinical trials for the treatment or prevention of cancer, there is substantial need for direct evaluation of HLA-A*0201-associated peptides from MART-1 and gp100 that are naturally processed and presented.
258	10417764	To that end, we have isolated peptides directly from HLA-A*0201 molecules of human melanoma cells and have determined that naturally processed epitopes for HLA-A*0201-restricted, melanoma-reactive CTLs include the nonamers MART-1(27-35) (AAGIGILTV), gp100(154-162) (KTWGQYWQV), gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA) and the decamer gp100(476-485) (VLYRYGSFSV).
259	10417764	HLA-A*0201-restricted CTLs from one melanoma patient who has survived metastatic disease recognized MART-1(27-35) (AAGIGILTV), gp100(280-288) (YLEPGPVTA) and gp100(154-162) (KTWGQYWQV) and were cross-reactive on longer peptides that contained these nonamer sequences.
260	10417764	Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
261	10417764	Melanoma-reactive human cytotoxic T lymphocytes (CTLs) mediate tumor regression in vivo through specific recognition of MHC-associated peptide epitopes, many of which are encoded by the melanocytic tissue differentiation proteins gp100/Pme117 and MART-1/Melan-A.
262	10417764	Especially where these peptides may be used in human clinical trials for the treatment or prevention of cancer, there is substantial need for direct evaluation of HLA-A*0201-associated peptides from MART-1 and gp100 that are naturally processed and presented.
263	10417764	To that end, we have isolated peptides directly from HLA-A*0201 molecules of human melanoma cells and have determined that naturally processed epitopes for HLA-A*0201-restricted, melanoma-reactive CTLs include the nonamers MART-1(27-35) (AAGIGILTV), gp100(154-162) (KTWGQYWQV), gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA) and the decamer gp100(476-485) (VLYRYGSFSV).
264	10417764	HLA-A*0201-restricted CTLs from one melanoma patient who has survived metastatic disease recognized MART-1(27-35) (AAGIGILTV), gp100(280-288) (YLEPGPVTA) and gp100(154-162) (KTWGQYWQV) and were cross-reactive on longer peptides that contained these nonamer sequences.
265	10537339	Immune responses were measured by release of IFN-gamma in an ELISA assay by effector cells after multiple restimulations of peripheral blood mononuclear cells in the presence of MART-1(27-35) peptide-pulsed antigen-presenting cells.
266	10605047	Serial FNA of the same lesions were performed in five HLA-A*0201 patients vaccinated with the emulsified melanoma Ag (MA) epitopes: MART-1:27-35; tyrosinase:368-376(370D); gp100:280-288(288V); and gp100:209-217 (210M).
267	10618430	Melan-A/MART-1(51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4(+) T cells.
268	10618430	The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8(+) cytotoxic T lymphocytes.
269	10618430	The Melan-A/MART-1(51-73) peptide was able to induce the in vitro expansion of specific CD4(+) T cells derived from normal DR4(+) donors or from DR4(+) patients with melanoma when pulsed onto autologous dendritic cells.
270	10618430	CD4(+) responder T cells specifically produced IFN-gamma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MART-1(51-73) peptide and DR4(+) melanoma target cells naturally expressing the Melan-A/MART-1 gene product.
271	10618430	Interestingly, CD4(+) T cell immunoreactivity against the Melan-A/MART-1(51-73) peptide typically coexisted with a high frequency of anti-Melan-A/MART-1(27-35) reactive CD8(+) T cells in freshly isolated blood harvested from HLA-A2(+)/DR4(+) patients with melanoma.
272	10618430	Taken together, these data support the use of this Melan-A/MART-1 DR4-restricted melanoma epitope in future immunotherapeutic trials designed to generate, augment, and quantitate specific CD4(+) T cell responses against melanoma in vivo.
273	10618430	Melan-A/MART-1(51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4(+) T cells.
274	10618430	The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8(+) cytotoxic T lymphocytes.
275	10618430	The Melan-A/MART-1(51-73) peptide was able to induce the in vitro expansion of specific CD4(+) T cells derived from normal DR4(+) donors or from DR4(+) patients with melanoma when pulsed onto autologous dendritic cells.
276	10618430	CD4(+) responder T cells specifically produced IFN-gamma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MART-1(51-73) peptide and DR4(+) melanoma target cells naturally expressing the Melan-A/MART-1 gene product.
277	10618430	Interestingly, CD4(+) T cell immunoreactivity against the Melan-A/MART-1(51-73) peptide typically coexisted with a high frequency of anti-Melan-A/MART-1(27-35) reactive CD8(+) T cells in freshly isolated blood harvested from HLA-A2(+)/DR4(+) patients with melanoma.
278	10618430	Taken together, these data support the use of this Melan-A/MART-1 DR4-restricted melanoma epitope in future immunotherapeutic trials designed to generate, augment, and quantitate specific CD4(+) T cell responses against melanoma in vivo.
279	10618430	Melan-A/MART-1(51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4(+) T cells.
280	10618430	The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8(+) cytotoxic T lymphocytes.
281	10618430	The Melan-A/MART-1(51-73) peptide was able to induce the in vitro expansion of specific CD4(+) T cells derived from normal DR4(+) donors or from DR4(+) patients with melanoma when pulsed onto autologous dendritic cells.
282	10618430	CD4(+) responder T cells specifically produced IFN-gamma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MART-1(51-73) peptide and DR4(+) melanoma target cells naturally expressing the Melan-A/MART-1 gene product.
283	10618430	Interestingly, CD4(+) T cell immunoreactivity against the Melan-A/MART-1(51-73) peptide typically coexisted with a high frequency of anti-Melan-A/MART-1(27-35) reactive CD8(+) T cells in freshly isolated blood harvested from HLA-A2(+)/DR4(+) patients with melanoma.
284	10618430	Taken together, these data support the use of this Melan-A/MART-1 DR4-restricted melanoma epitope in future immunotherapeutic trials designed to generate, augment, and quantitate specific CD4(+) T cell responses against melanoma in vivo.
285	10618430	Melan-A/MART-1(51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4(+) T cells.
286	10618430	The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8(+) cytotoxic T lymphocytes.
287	10618430	The Melan-A/MART-1(51-73) peptide was able to induce the in vitro expansion of specific CD4(+) T cells derived from normal DR4(+) donors or from DR4(+) patients with melanoma when pulsed onto autologous dendritic cells.
288	10618430	CD4(+) responder T cells specifically produced IFN-gamma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MART-1(51-73) peptide and DR4(+) melanoma target cells naturally expressing the Melan-A/MART-1 gene product.
289	10618430	Interestingly, CD4(+) T cell immunoreactivity against the Melan-A/MART-1(51-73) peptide typically coexisted with a high frequency of anti-Melan-A/MART-1(27-35) reactive CD8(+) T cells in freshly isolated blood harvested from HLA-A2(+)/DR4(+) patients with melanoma.
290	10618430	Taken together, these data support the use of this Melan-A/MART-1 DR4-restricted melanoma epitope in future immunotherapeutic trials designed to generate, augment, and quantitate specific CD4(+) T cell responses against melanoma in vivo.
291	10618430	Melan-A/MART-1(51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4(+) T cells.
292	10618430	The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8(+) cytotoxic T lymphocytes.
293	10618430	The Melan-A/MART-1(51-73) peptide was able to induce the in vitro expansion of specific CD4(+) T cells derived from normal DR4(+) donors or from DR4(+) patients with melanoma when pulsed onto autologous dendritic cells.
294	10618430	CD4(+) responder T cells specifically produced IFN-gamma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MART-1(51-73) peptide and DR4(+) melanoma target cells naturally expressing the Melan-A/MART-1 gene product.
295	10618430	Interestingly, CD4(+) T cell immunoreactivity against the Melan-A/MART-1(51-73) peptide typically coexisted with a high frequency of anti-Melan-A/MART-1(27-35) reactive CD8(+) T cells in freshly isolated blood harvested from HLA-A2(+)/DR4(+) patients with melanoma.
296	10618430	Taken together, these data support the use of this Melan-A/MART-1 DR4-restricted melanoma epitope in future immunotherapeutic trials designed to generate, augment, and quantitate specific CD4(+) T cell responses against melanoma in vivo.
297	10618430	Melan-A/MART-1(51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4(+) T cells.
298	10618430	The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8(+) cytotoxic T lymphocytes.
299	10618430	The Melan-A/MART-1(51-73) peptide was able to induce the in vitro expansion of specific CD4(+) T cells derived from normal DR4(+) donors or from DR4(+) patients with melanoma when pulsed onto autologous dendritic cells.
300	10618430	CD4(+) responder T cells specifically produced IFN-gamma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MART-1(51-73) peptide and DR4(+) melanoma target cells naturally expressing the Melan-A/MART-1 gene product.
301	10618430	Interestingly, CD4(+) T cell immunoreactivity against the Melan-A/MART-1(51-73) peptide typically coexisted with a high frequency of anti-Melan-A/MART-1(27-35) reactive CD8(+) T cells in freshly isolated blood harvested from HLA-A2(+)/DR4(+) patients with melanoma.
302	10618430	Taken together, these data support the use of this Melan-A/MART-1 DR4-restricted melanoma epitope in future immunotherapeutic trials designed to generate, augment, and quantitate specific CD4(+) T cell responses against melanoma in vivo.
303	10687135	Reduced recognition of metastatic melanoma cells by autologous MART-1 specific CTL: relationship to TAP expression.
304	10687135	Tumor infiltrating lymphocytes from a patient with melanoma were isolated, expanded in vitro in the presence of interleukin-2, and tested for cytotoxicity against HLA-A2 positive, MART-1 positive autologous tumor cells, an HLA-A2-positive, MART-1 positive melanoma cell line (Mel-501), and HLA-A2-negative melanoma cells.
305	10687135	To address whether the deficiency in autologous tumor recognition might be related to a deficiency in Ag presentation, we screened for the presence of TAP1 and TAP2 transcripts by polymerase chain reaction, Southern blotting, and scanning densitometry using sequence-specific primers and probes.
306	10687135	Both TAP1 and TAP2 expression levels in the autologous tumor were minimal, yet were upregulated 7- to 18-fold, respectively, by interferon-gamma.
307	10687135	Reduced recognition of metastatic melanoma cells by autologous MART-1 specific CTL: relationship to TAP expression.
308	10687135	Tumor infiltrating lymphocytes from a patient with melanoma were isolated, expanded in vitro in the presence of interleukin-2, and tested for cytotoxicity against HLA-A2 positive, MART-1 positive autologous tumor cells, an HLA-A2-positive, MART-1 positive melanoma cell line (Mel-501), and HLA-A2-negative melanoma cells.
309	10687135	To address whether the deficiency in autologous tumor recognition might be related to a deficiency in Ag presentation, we screened for the presence of TAP1 and TAP2 transcripts by polymerase chain reaction, Southern blotting, and scanning densitometry using sequence-specific primers and probes.
310	10687135	Both TAP1 and TAP2 expression levels in the autologous tumor were minimal, yet were upregulated 7- to 18-fold, respectively, by interferon-gamma.
311	10687138	The response was mediated by major histocompatibility complex class I-restricted cytotoxic T lymphocytes specific for MART-1 antigen, which produced high levels of interferon-gamma when reexposed to MART-1 in vitro and lysed targets in a calcium-dependent mechanism suggestive of perforin/granzyme B lysis.
312	10702485	To establish that the assay is able to detect the T-cell precursor cells responsive to the vaccine, we used CD8(+) T-cell populations positively selected from PBMC of HLA-A2(+) patients with metastatic melanoma, who were treated with dendritic cell-based vaccines containing gp100, MELAN-A/MART-1, tyrosinase, and influenza virus matrix peptides.
313	10706736	In vitro priming with adenovirus/gp100 antigen-transduced dendritic cells reveals the epitope specificity of HLA-A*0201-restricted CD8+ T cells in patients with melanoma.
314	10706736	Replication-deficient recombinant adenovirus (Ad) encoding human gp100 or MART-1 melanoma Ag was used to transduce human dendritic cells (DC) ex vivo as a model system for cancer vaccine therapy.
315	10706736	Thus, patients with metastatic melanoma are not tolerant to gp100 Ag based on the detection of CD8+ T cells specific for multiple HLA-A*0201-restricted, gp100-derived epitopes.
316	10752474	Melanoma-reactive HLA-A x 0201-restricted cytotoxic T lymphocyte (CTL) lines generated in vitro lyse autologous and HLA-matched allogeneic melanoma cells and recognize multiple shared peptide antigens from tyrosinase, MART-1, and Pme117/gp100.
317	10752474	All four are deficient in expression of the melanocytic differentiation proteins (MDP) tyrosinase, Pme117/gp100, gp75/ trp-1, and MART-1/Melan-A.
318	10752474	Melanoma-reactive HLA-A x 0201-restricted cytotoxic T lymphocyte (CTL) lines generated in vitro lyse autologous and HLA-matched allogeneic melanoma cells and recognize multiple shared peptide antigens from tyrosinase, MART-1, and Pme117/gp100.
319	10752474	All four are deficient in expression of the melanocytic differentiation proteins (MDP) tyrosinase, Pme117/gp100, gp75/ trp-1, and MART-1/Melan-A.
320	10760827	We have shown that the sequential use of early-acting hematopoietic growth factors, stem cell factor, IL-3 and IL-6, followed by differentiation with IL-4 and granulocyte-macrophage colony-stimulating factor allows the in vitro generation of large numbers of immature DCs from CD34(+) peripheral blood progenitor cells.
321	10760827	Fourteen HLA-A1(+) or HLA-A2(+) patients received at least 4 i.v. infusions of 5 x 10(6) to 5 x 10(7) DCs pulsed with a pool of peptides including either MAGE-1, MAGE-3 (HLA-A1) or Melan-A, gp100, tyrosinase (HLA-A2), depending on the HLA haplotype.
322	10786687	Genetic immunization with a single injection of dendritic cells (DCs) expressing a model melanoma antigen generates antigen-specific, MHC-restricted, protective immune responses.
323	10786687	In conclusion, C3H mice but not C57BL/6 mice receiving multiple vaccinations with DCs expressing the MART-1 tumor antigen show decreased protection associated with deviation from a type 1 to a type 2 cytokine response attributable to a Fas-receptor mediated clearance of antigen-specific IFN-gamma-producing cells.
324	10838667	MART-1, a melanoma antigen recognized by T cells-1, is a melanocyte lineage-differentiation antigen expressed only in melanocytes and melanoma cells.
325	10838667	We have produced and purified Escherichia coli recombinant MART-1 protein using a glutathione-S-transferase fusion protein expression system.
326	10838667	The glutathione-S-transferase fusion method yielded approximately 200 micrograms MART-1 per 2-L bacterial culture, enough to coat 100 ELISA plates.
327	10838667	MART-1, a melanoma antigen recognized by T cells-1, is a melanocyte lineage-differentiation antigen expressed only in melanocytes and melanoma cells.
328	10838667	We have produced and purified Escherichia coli recombinant MART-1 protein using a glutathione-S-transferase fusion protein expression system.
329	10838667	The glutathione-S-transferase fusion method yielded approximately 200 micrograms MART-1 per 2-L bacterial culture, enough to coat 100 ELISA plates.
330	10838667	MART-1, a melanoma antigen recognized by T cells-1, is a melanocyte lineage-differentiation antigen expressed only in melanocytes and melanoma cells.
331	10838667	We have produced and purified Escherichia coli recombinant MART-1 protein using a glutathione-S-transferase fusion protein expression system.
332	10838667	The glutathione-S-transferase fusion method yielded approximately 200 micrograms MART-1 per 2-L bacterial culture, enough to coat 100 ELISA plates.
333	10916759	Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100.
334	10916759	Furthermore, DC-like function can be elicited from peripheral blood monocytes cultured in vitro with interleukin-4 and granulocyte-macrophage colony-stimulating factor.
335	10916759	The DCs were generated by 5- to 7-day incubation in interleukin-4 (1,000 U/mL) and granulocyte-macrophage colony-stimulating factor (1,000 U/mL) of peripheral blood monocytes obtained by leukapheresis.
336	10916759	Before administration, the DCs were pulsed separately with the HLA-A*0201-associated melanoma epitopes MART-1(27-35) and gp-100-209-2M.
337	10916759	Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100.
338	10916759	Furthermore, DC-like function can be elicited from peripheral blood monocytes cultured in vitro with interleukin-4 and granulocyte-macrophage colony-stimulating factor.
339	10916759	The DCs were generated by 5- to 7-day incubation in interleukin-4 (1,000 U/mL) and granulocyte-macrophage colony-stimulating factor (1,000 U/mL) of peripheral blood monocytes obtained by leukapheresis.
340	10916759	Before administration, the DCs were pulsed separately with the HLA-A*0201-associated melanoma epitopes MART-1(27-35) and gp-100-209-2M.
341	10940901	Synthetic insertion signal sequences enhance MHC class I presentation of a peptide from the melanoma antigen MART-1.
342	10940901	We report here that the addition of synthetic signal sequences at the N terminus, but not at the C terminus, of an epitope from the human melanoma antigen MART-1 greatly enhances its presentation in both TAP-deficient and TAP-expressing cells.
343	10940901	Synthetic insertion signal sequences enhance MHC class I presentation of a peptide from the melanoma antigen MART-1.
344	10940901	We report here that the addition of synthetic signal sequences at the N terminus, but not at the C terminus, of an epitope from the human melanoma antigen MART-1 greatly enhances its presentation in both TAP-deficient and TAP-expressing cells.
345	10994477	These antigens include MAGE 1 and 3, tyrosinase, MelanA/MART-1 and gp100.
346	11033019	Thirty-one patients with melanoma were immunized to a polyvalent vaccine containing multiple antigens, including MAGE-3, Melan A/MART-1, gp100 and tyrosinase.
347	11092048	PCR was used to detect melanoma cells that expressed the melanoma-associated antigens MART-1, MAGE-3, tyrosinase and/or gp100 in 91 patients with melanoma.
348	11092048	The vaccine contains multiple melanoma-associated antigens including MART-1, MAGE-3, tyrosinase and gp100.
349	11092048	PCR was used to detect melanoma cells that expressed the melanoma-associated antigens MART-1, MAGE-3, tyrosinase and/or gp100 in 91 patients with melanoma.
350	11092048	The vaccine contains multiple melanoma-associated antigens including MART-1, MAGE-3, tyrosinase and gp100.
351	11104796	In this study, we show that human DCs derived from monocytes and loaded with killed melanoma cells prime naive CD45RA(+)CD27(+)CD8(+) T cells against the four shared melanoma antigens: MAGE-3, gp100, tyrosinase, and MART-1.
352	11254719	We studied the CTL response induced in HLA-A*0201/K(b) transgenic mice immunized with peptides derived from two melanoma-associated differentiation Ags, the HLA-A*0201-restricted decapeptide Melan-A(26--35) substituted at position 2 and the K(b)-restricted tyrosinase-related protein 2(181--188) T cell epitope.
353	11254719	Moreover, the CTL response generated against the tyrosinase-related protein 2(181-188) peptide in presence of P40 is associated with tumor protection in two different experimental models and is independent of the presence of CD4(+) T lymphocytes.
354	11300475	Here we report that the frequency of circulating CD8+ T cells directed against the Melan-A/MART-1 Ag increased >20-fold in an HLA-A2 melanoma patient immunized repeatedly with the corresponding antigenic peptide, as assessed by staining with HLA-A2/peptide tetramers.
355	11300475	As assessed by ELISPOT assays and intracellular staining, the absolute number of Melan-A-specific cells able to secrete IFN-gamma increased >50-fold upon vaccination.
356	11300475	Here we report that the frequency of circulating CD8+ T cells directed against the Melan-A/MART-1 Ag increased >20-fold in an HLA-A2 melanoma patient immunized repeatedly with the corresponding antigenic peptide, as assessed by staining with HLA-A2/peptide tetramers.
357	11300475	As assessed by ELISPOT assays and intracellular staining, the absolute number of Melan-A-specific cells able to secrete IFN-gamma increased >50-fold upon vaccination.
358	11320407	Importantly, transfected epidermal Langerhans cells can efficiently present a peptide derived from the transgenic melanoma antigen MART-1 to a MART-1-specific CTL.
359	11410873	Immature and mature DCs were separately pulsed with a peptide derived from tyrosinase, MelanA/MART-1 or MAGE-1 and a recall antigen.
360	11449353	Comprehensive analysis of the frequency of recognition of melanoma-associated antigen (MAA) by CD8 melanoma infiltrating lymphocytes (TIL): implications for immunotherapy.
361	11449353	Melanosomal proteins were recognized by 19 TIL populations and the most prominent responses against these proteins were directed against Melan-A/MART-1 (mainly in association with HLA-A*0201) and gp100 (in association with diverse HLA contexts).
362	11459172	In order to construct an immunogenic cellular vaccine, we transduced three HLA-A*0201 human melanoma lines, selected for expression of classes I and II HLA, adhesion molecules and the T cell-defined melanoma antigens Melan/MART-1, gp100 and tyrosinase, with both interleukin-2 (IL-2) and B7-1 genes by the use of a polycistronic retroviral vector.
363	11459172	From a functional point of view, expression of both genes in melanoma lines: (1) improved the response of anti-melanoma cytotoxic T lymphocytes (CTL) over singly transduced or untransduced melanoma cells when subthreshold levels of MHC-peptide complexes were expressed by melanoma cells; (2) conferred a distinct advantage in the ability to stimulate cytotoxicity and interferon-gamma release by autologous and/or HLA-A*0201-compatible allogeneic lymphocytes; (3) allowed the generation of a high number of specific CTL by in vitro stimulation of lymphocytes of HLA-A*0201-melanoma patients.
364	11466405	Cocultures of ALVAC MART-1-infected and uninfected DC are able to induce MART-1-specific T cell immune responses, as assessed by HLA class I/peptide tetramer binding, IFN-gamma ELISPOT assays, and cytotoxicity tests.
365	11514604	We have previously shown that small B16 melanomas can be successfully treated using a combination of anti-cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibody with a granulocyte/macrophage colony-stimulating factor (GM-CSF) producing irradiated tumor cell vaccine.
366	11514604	Analysis of the response in successfully treated mice revealed elevated levels of CD8(+) T cells specific for a nonameric peptide consisting of residues 180-188 of the melanocyte differentiation antigen tyrosinase-related protein (TRP)2.
367	11514604	There was no evidence of reactivity to the melanocyte antigens gp100, tyrosinase, Mart1/MelanA, or TRP1.
368	11514604	In particular, if mice received a prophylactic vaccine consisting of anti-CTLA-4 and B16-GM-CSF before tumor challenge, full protection was obtained even in the absence of CD8(+) T cells.
369	11522640	Eighteen HLA A*0201(+) patients with metastatic melanoma received injections s.c. of CD34(+)progenitor-derived autologous dendritic cells (DCs), which included Langerhans cells.
370	11522640	DCs were pulsed with peptides derived from four melanoma antigens [(MelAgs) MelanA/MART-1, tyrosinase, MAGE-3, and gp100], as well as influenza matrix peptide (Flu-MP) and keyhole limpet hemocyanin (KLH) as control antigens.
371	11565834	An autologous melanoma cell line selected for loss of expression of the immunodominant MART-1 and gp100 antigens was initially used to carry out a mixed lymphocyte tumor culture (MLTC) in a patient who expressed the human leukocyte antigen (HLA)-AI and HLA-A2 class I major histocompatibility complex alleles.
372	11730853	CD40 ligand and lipopolysaccharide enhance the in vitro generation of melanoma-reactive T-cells.
373	11730853	We have developed an efficient and reproducible method for detecting tumor-specific T cells by optimizing the activation of antigen presenting cells (APC) in peripheral blood mononuclear cells (PBMC) of metastatic melanoma patients with soluble trimeric CD40-ligand (CD40L) or lipopolysaccharide (LPS).
374	11730853	This method significantly improved the generation of Melan-A/MART-1:27-35 and Melan-A/MART-1:26-35(27L) peptide/tumor-specific cells as well as lower frequency tyrosinase:368-376(370D) specific T cells from the PBMC of melanoma patients.
375	11730853	Additionally, PBMC activation improved the detection of tumor-specific precursors from melanoma patients previously immunized with peptides derived from Melan-A/MART-1, tyrosinase and gp100.
376	11730853	CD40 ligand and lipopolysaccharide enhance the in vitro generation of melanoma-reactive T-cells.
377	11730853	We have developed an efficient and reproducible method for detecting tumor-specific T cells by optimizing the activation of antigen presenting cells (APC) in peripheral blood mononuclear cells (PBMC) of metastatic melanoma patients with soluble trimeric CD40-ligand (CD40L) or lipopolysaccharide (LPS).
378	11730853	This method significantly improved the generation of Melan-A/MART-1:27-35 and Melan-A/MART-1:26-35(27L) peptide/tumor-specific cells as well as lower frequency tyrosinase:368-376(370D) specific T cells from the PBMC of melanoma patients.
379	11730853	Additionally, PBMC activation improved the detection of tumor-specific precursors from melanoma patients previously immunized with peptides derived from Melan-A/MART-1, tyrosinase and gp100.
380	11801657	Mice transgenic for a chimeric MHC class I molecule were immunized with a peptide analog of MART-1/Melan-A(26-35) in the presence of CpG ODN alone or CpG ODN emulsified in IFA.
381	11874634	The immunization protocol consisted of the administration of psoralen-UV-treated and replication-incompetent recombinant vaccinia virus encoding the three immunodominant HLA-A*0201-restricted epitopes Melan-A(27-35), gp100(280-288), and tyrosinase(1-9) together with two costimulatory molecules, B7.1 and B7.2, in the context of systemic granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment.
382	11920589	Peptide-specific CD8+ T-cell evolution in vivo: response to peptide vaccination with Melan-A/MART-1.
383	11920589	We have longitudinally followed CD8+ T-cell responses in 3 melanoma patients who were immunized with peptides derived from Melan-A/MART-1.
384	11920589	At least in a single patient, T cells binding to the AAGIGILTV epitope were detected in naive, precursor (CD45RA+/CCR7+) CD8+ T cells, and CD8+ T cells binding to the analog ELAGIGILTV peptide were identified in the terminally differentiated (CD45RA+/CCR7-) T-cell subset.
385	11920589	The TCR repertoire reactive with Melan-A/MART-1 peptide epitopes was broadened during vaccination and exhibited a different profile of cytokine release after specific stimulation: tetramer-binding T cells from 2/3 patients secreted granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon-gamma but not interleukin-2 (IL-2) in response to Melan-A/MART-1 peptides.
386	11920589	Peptide-specific CD8+ T-cell evolution in vivo: response to peptide vaccination with Melan-A/MART-1.
387	11920589	We have longitudinally followed CD8+ T-cell responses in 3 melanoma patients who were immunized with peptides derived from Melan-A/MART-1.
388	11920589	At least in a single patient, T cells binding to the AAGIGILTV epitope were detected in naive, precursor (CD45RA+/CCR7+) CD8+ T cells, and CD8+ T cells binding to the analog ELAGIGILTV peptide were identified in the terminally differentiated (CD45RA+/CCR7-) T-cell subset.
389	11920589	The TCR repertoire reactive with Melan-A/MART-1 peptide epitopes was broadened during vaccination and exhibited a different profile of cytokine release after specific stimulation: tetramer-binding T cells from 2/3 patients secreted granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon-gamma but not interleukin-2 (IL-2) in response to Melan-A/MART-1 peptides.
390	11920589	Peptide-specific CD8+ T-cell evolution in vivo: response to peptide vaccination with Melan-A/MART-1.
391	11920589	We have longitudinally followed CD8+ T-cell responses in 3 melanoma patients who were immunized with peptides derived from Melan-A/MART-1.
392	11920589	At least in a single patient, T cells binding to the AAGIGILTV epitope were detected in naive, precursor (CD45RA+/CCR7+) CD8+ T cells, and CD8+ T cells binding to the analog ELAGIGILTV peptide were identified in the terminally differentiated (CD45RA+/CCR7-) T-cell subset.
393	11920589	The TCR repertoire reactive with Melan-A/MART-1 peptide epitopes was broadened during vaccination and exhibited a different profile of cytokine release after specific stimulation: tetramer-binding T cells from 2/3 patients secreted granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon-gamma but not interleukin-2 (IL-2) in response to Melan-A/MART-1 peptides.
394	11937585	To gain insight into these questions, we performed a functional and structural longitudinal analysis of the TCR of circulating CD8(+) T cells specific for the HLA-A2-restricted immunodominant epitope from the melanocyte differentiation Ag Melan-A in a melanoma patient who developed a vigorous and sustained Ag-specific T cell response following vaccination with the corresponding synthetic peptide.
395	11937585	Ex vivo analysis of the clonal composition of Melan-A-specific CD8(+) T cells at different time points during vaccination revealed that the response was the result of asynchronous expansion of several distinct T cell clones.
396	11937585	To gain insight into these questions, we performed a functional and structural longitudinal analysis of the TCR of circulating CD8(+) T cells specific for the HLA-A2-restricted immunodominant epitope from the melanocyte differentiation Ag Melan-A in a melanoma patient who developed a vigorous and sustained Ag-specific T cell response following vaccination with the corresponding synthetic peptide.
397	11937585	Ex vivo analysis of the clonal composition of Melan-A-specific CD8(+) T cells at different time points during vaccination revealed that the response was the result of asynchronous expansion of several distinct T cell clones.
398	12056962	Hypopigmentation associated with an adenovirus-mediated gp100/MART-1-transduced dendritic cell vaccine for metastatic melanoma.
399	12057601	The second construct NS1-Mela 2 carrying both Tyrosinase (369-377Da) and Melan-A/Mart-1 (27-35) epitopes induced a weak Tyrosinase-specific CTL response in mice but failed to induce specific CTL responses against the Melan-A/Mart-1 (27-35) epitope in the tested mice.
400	12103339	Melan-A/MART-1-specific CD8 T cells: from thymus to tumor.
401	12192536	Stably growing hybrid antigen-presenting cells (HAPC) expressing HLA-DR and HLA-A2 (or HLA-A30/31), and melanoma-associated antigens (MART-1, gp100) were selected by a double strategy of immunomagnetic MACS and neomycin selection.
402	12192536	Expression of melanoma-associated antigens (MART-1, gp100) in hybrid cells was determined by reverse transcription-polymerase chain reaction (RT-PCR).
403	12192536	HLA-restricted antigen-specific presentation of melanoma antigens was demonstrated by killing of semi-allogenic HAPC by HLA-A2-restricted MART-1 or gp100-specific cytotoxic T lymphocyte (CTL) clones.
404	12192536	Stably growing hybrid antigen-presenting cells (HAPC) expressing HLA-DR and HLA-A2 (or HLA-A30/31), and melanoma-associated antigens (MART-1, gp100) were selected by a double strategy of immunomagnetic MACS and neomycin selection.
405	12192536	Expression of melanoma-associated antigens (MART-1, gp100) in hybrid cells was determined by reverse transcription-polymerase chain reaction (RT-PCR).
406	12192536	HLA-restricted antigen-specific presentation of melanoma antigens was demonstrated by killing of semi-allogenic HAPC by HLA-A2-restricted MART-1 or gp100-specific cytotoxic T lymphocyte (CTL) clones.
407	12192536	Stably growing hybrid antigen-presenting cells (HAPC) expressing HLA-DR and HLA-A2 (or HLA-A30/31), and melanoma-associated antigens (MART-1, gp100) were selected by a double strategy of immunomagnetic MACS and neomycin selection.
408	12192536	Expression of melanoma-associated antigens (MART-1, gp100) in hybrid cells was determined by reverse transcription-polymerase chain reaction (RT-PCR).
409	12192536	HLA-restricted antigen-specific presentation of melanoma antigens was demonstrated by killing of semi-allogenic HAPC by HLA-A2-restricted MART-1 or gp100-specific cytotoxic T lymphocyte (CTL) clones.
410	12386826	Immunosuppressive effects of interleukin-12 coexpression in melanoma antigen gene-modified dendritic cell vaccines.
411	12386826	In a series of experiments immunizing mice with DC cotransduced with MART-1 and IL-12, antitumor protection and antigen-specific splenocyte cytotoxicity and interferon gamma production inversely correlated with the amount of IL-12 produced by DC.
412	12576434	Activation of human melanoma reactive CD8+ T cells by vaccination with an immunogenic peptide analog derived from Melan-A/melanoma antigen recognized by T cells-1.
413	12645955	Adoptive transfer of an anti-MART-1(27-35)-specific CD8+ T cell clone leads to immunoselection of human melanoma antigen-loss variants in SCID mice.
414	12645955	In this study we investigated the level of efficacy of a MART-1/Melan-A-specific CD8+ T cell clone against its autologous melanoma in a severe combined immunodeficiency (SCID) mouse model, in which the tumor cells expressed in vivo heterogeneous and suboptimal levels of MART-1.
415	12645955	Adoptive transfer of an anti-MART-1(27-35)-specific CD8+ T cell clone leads to immunoselection of human melanoma antigen-loss variants in SCID mice.
416	12645955	In this study we investigated the level of efficacy of a MART-1/Melan-A-specific CD8+ T cell clone against its autologous melanoma in a severe combined immunodeficiency (SCID) mouse model, in which the tumor cells expressed in vivo heterogeneous and suboptimal levels of MART-1.
417	12670905	Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues.
418	12670905	We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release.
419	12670905	HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope.
420	12670905	Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope.
421	12670905	A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions.
422	12670905	A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions.
423	12670905	To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding).
424	12670905	T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope.
425	12670905	This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2.
426	12670905	Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues.
427	12670905	We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release.
428	12670905	HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope.
429	12670905	Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope.
430	12670905	A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions.
431	12670905	A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions.
432	12670905	To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding).
433	12670905	T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope.
434	12670905	This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2.
435	12670905	Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues.
436	12670905	We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release.
437	12670905	HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope.
438	12670905	Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope.
439	12670905	A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions.
440	12670905	A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions.
441	12670905	To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding).
442	12670905	T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope.
443	12670905	This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2.
444	12670905	Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues.
445	12670905	We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release.
446	12670905	HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope.
447	12670905	Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope.
448	12670905	A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions.
449	12670905	A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions.
450	12670905	To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding).
451	12670905	T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope.
452	12670905	This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2.
453	12670905	Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues.
454	12670905	We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release.
455	12670905	HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope.
456	12670905	Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope.
457	12670905	A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions.
458	12670905	A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions.
459	12670905	To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding).
460	12670905	T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope.
461	12670905	This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2.
462	12670905	Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues.
463	12670905	We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release.
464	12670905	HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope.
465	12670905	Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope.
466	12670905	A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions.
467	12670905	A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions.
468	12670905	To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding).
469	12670905	T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope.
470	12670905	This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2.
471	12670905	Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues.
472	12670905	We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release.
473	12670905	HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope.
474	12670905	Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope.
475	12670905	A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions.
476	12670905	A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions.
477	12670905	To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding).
478	12670905	T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope.
479	12670905	This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2.
480	12670905	Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues.
481	12670905	We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release.
482	12670905	HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope.
483	12670905	Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope.
484	12670905	A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions.
485	12670905	A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions.
486	12670905	To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding).
487	12670905	T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope.
488	12670905	This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2.
489	12692260	Here we report the purification and characterization of one of these down-regulatory factors, the cytokine, oncostatin M (OSM), which transmits its signal via the gp130 cell surface receptor, resulting in the selective down-modulation of the melanocyte lineage antigens: Melan-A/MART-1, gp100, tyrosinase, tyrosinase-related proteins 1 and 2, and the M isoform of microphthalmia transcription factor.
490	12734382	DC-888mel hybrids efficiently presented HLA-A*0201-restricted epitopes from the melanoma Ags MART-1, gp100, tyrosinase, and tyrosinase-related protein 2 as evaluated by specific cytokine secretion from six distinct CTL lines.
491	12734382	In contrast, DCs could not cross-present MHC class I-restricted epitopes after exogenously loading with gp100 protein.
492	12734382	DC-888mel hybrids also presented HLA-DR beta 1*0401- and HLA-DR beta 1*0701-restricted peptides from gp100 to CD4(+) T cell populations.
493	12734382	Therefore, fusions of DCs and tumor cells express both MHC class I- and class II-restricted tumor-associated epitopes and may be useful for the induction of tumor-reactive CD8(+) and CD4(+) T cells in vitro and in human vaccination trials.
494	12767067	Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: presentation of MART1 to CD8+ T cells.
495	12767067	Furthermore, we show that fixed E. coli/LLO expressing the well-characterised human melanoma antigen, MART1, efficiently deliver the HLA-A2-restricted MART1(27-35) epitope for processing and presentation on human MoDCs, suggesting the potential of this system as a novel strategy for human tumour immunotherapy.
496	12767067	Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: presentation of MART1 to CD8+ T cells.
497	12767067	Furthermore, we show that fixed E. coli/LLO expressing the well-characterised human melanoma antigen, MART1, efficiently deliver the HLA-A2-restricted MART1(27-35) epitope for processing and presentation on human MoDCs, suggesting the potential of this system as a novel strategy for human tumour immunotherapy.
498	12824506	In addition, tumors were examined for expression of vimentin, cytokeratin, smooth muscle actin, desmin, melan A, neural cell adhesion molecule, S-100, glial fibrillary acidic protein, nerve growth factor receptor, and collagen type IV.
499	12824506	On the basis of collagen type IV and crystallin alpha A immunopositivity, we established that three of nine tumors were of lens epithelial origin.
500	12824506	Expression of desmin and smooth muscle actin identified one tumor as a leiomyosarcoma.
501	12837633	[Contribution to the detection of Melan-A/Mart-1 specific CD8+ T cells in surgery of melanoma.
502	12837633	In the present work, we used tetrameric technology to detect expanded populations of tumor specific CD8+ Tcells specific of Melan-A/Mart-1 Antigen have been quantified using flow cytometry.
503	12837633	[Contribution to the detection of Melan-A/Mart-1 specific CD8+ T cells in surgery of melanoma.
504	12837633	In the present work, we used tetrameric technology to detect expanded populations of tumor specific CD8+ Tcells specific of Melan-A/Mart-1 Antigen have been quantified using flow cytometry.
505	12862418	Biopsies of accessible tumors showed infiltration with CD4+ and CD8+ lymphocytes capable of lysing Melan-A peptide-pulsed targets in vitro.
506	12928369	Through rapid culture techniques that prepared either mature, CD83+ DC1 or DC2 from CD14+ monocytes in only 2 days followed by a single 6-7 day DC-T cell coculture, we sensitized normal donor CD8+ T cells to tumor Ags (HER-2/neu, MART-1, and gp100) such that peptide Ag-specific lymphocytes constituted up to 16% of the total CD8+ population.
507	12973032	The authors vaccinated 18 HLA A*0201+ patients with stage IV melanoma with CD34 HPC-derived DCs pulsed with six antigens: influenza matrix peptide (Flu-MP), KLH, and peptides derived from the four melanoma antigens: MART-1/Melan A, gp100, tyrosinase, and MAGE-3.
508	12973032	A single DC vaccination was sufficient for induction of KLH-specific CD4 T-cell responses in five patients and Flu-MP-specific CD8 T-cell responses in eight patients.
509	12973032	Thus, a single injection of CD34 HPC-derived DCs can lead to rapid immune response to CD4 epitopes or to melanoma antigens.
510	14500402	In this study using the Melan-A/MART-1(27-35) peptide as a model for self but melanoma-associated antigen-against which human hosts often harbor CD8(+) CTL precursors with high frequencies-we confirm that although immature dendritic cells (iDCs) are inefficient antigen presenting cells (APCs), fully activated DCs efficiently activate melanoma epitope-specific CD8(+) CTL precursors, in vitro.
511	14500642	HLA-A*0201-restricted CD8(+) T cells recognizing Ags expressed in human melanoma (melanoma Ag recognized by T cell-1 (MART-1)/melanoma Ag A (Melan-A)) or colon carcinoma (carcinoembryonic Ag (CEA)/epithelial cell adhesion molecule (EpCAM)) were triggered to release IFN-gamma and to mediate cytotoxic activity by HLA-A*0201-matched APCs pulsed with hsp96 purified from tumor cells expressing the relevant Ag.
512	14500642	Immunization with autologous tumor-derived hsp96 induced a significant increase in the recognition of MART-1/Melan-A(27-35) in three of five HLA-A*0201 melanoma patients, and of CEA(571-579) and EpCAM(263-271) in two of five HLA-A*0201 colon carcinoma patients, respectively, as detected by ELISPOT and HLA/tetramer staining.
513	14500642	HLA-A*0201-restricted CD8(+) T cells recognizing Ags expressed in human melanoma (melanoma Ag recognized by T cell-1 (MART-1)/melanoma Ag A (Melan-A)) or colon carcinoma (carcinoembryonic Ag (CEA)/epithelial cell adhesion molecule (EpCAM)) were triggered to release IFN-gamma and to mediate cytotoxic activity by HLA-A*0201-matched APCs pulsed with hsp96 purified from tumor cells expressing the relevant Ag.
514	14500642	Immunization with autologous tumor-derived hsp96 induced a significant increase in the recognition of MART-1/Melan-A(27-35) in three of five HLA-A*0201 melanoma patients, and of CEA(571-579) and EpCAM(263-271) in two of five HLA-A*0201 colon carcinoma patients, respectively, as detected by ELISPOT and HLA/tetramer staining.
515	14577912	We performed a phase I/II clinical trial in metastatic melanoma patients with an ultraviolet (UV)-inactivated nonreplicating recombinant vaccinia virus enabling the expression, from a single construct, of endoplasmic reticulum-targeted HLA-A0201-restricted Melan-A/MART-1(27-35), gp100(280-288), and tyrosinase(1-9) epitopes, together with CD80 and CD86 costimulatory proteins.
516	14577912	Corresponding soluble peptides were used to boost responses and granulocyte-macrophage colony-stimulating factor was used as systemic adjuvant.
517	14580186	Peptide NY-ESO-1(157-165) was remarkably immunogenic and induced a CD8+ T cell response detectable ex vivo at an early time point of the vaccination protocol.
518	14580186	A CD8+ T cell response to the peptide analog Melan-A(26-35 A27L) was also detectable ex vivo at a later time point, whereas CD8+ T cells specific for peptide tyrosinase(368-376) were detected only after in vitro peptide stimulation.
519	14600790	Nineteen patients received DCs plus autologous lysates and 14 patients DCs plus peptides from the melanoma antigens MAGE-3.A2, tyrosinase, gp100, and MART-1.
520	14600790	DCs were produced from adherent cells in blood lymphocytes (monocytic DCs), grown in IL-4 and GM-CSF without a maturation step.
521	14609222	DCs were pulsed with MART1, tyrosinase, MAGE3, gp100 and Flu-MP peptides, and KLH.
522	14634146	We previously described HLA-B35-restricted melanoma tumor-infiltrating lymphocyte responses to frequently expressed melanoma-associated Ags: tyrosinase, Melan-A/MART-1, gp100, MAGE-A3/MAGE-A6, and NY-ESO-1.
523	14634146	In particular, the HLA-B35-restricted Melan-A epitope is mimicked by the peptide 26-35, already known as the most immunodominant melanoma epitope in the HLA-A*0201 context.
524	14634146	We previously described HLA-B35-restricted melanoma tumor-infiltrating lymphocyte responses to frequently expressed melanoma-associated Ags: tyrosinase, Melan-A/MART-1, gp100, MAGE-A3/MAGE-A6, and NY-ESO-1.
525	14634146	In particular, the HLA-B35-restricted Melan-A epitope is mimicked by the peptide 26-35, already known as the most immunodominant melanoma epitope in the HLA-A*0201 context.
526	14726959	Additionally, these SLC-secreting DC were found to be viable to a large extent despite the cytopathic effect inherent in adenoviral gene transfer and, most importantly, functional as determined by their ability to prime autologous T cells to a known melanoma-associated antigen, MART-1.
527	14871300	Melanoma antigen recognized by T cell 1 (MART-1) is regarded as a candidate peptide for vaccination against malignant melanoma, and it is of importance to develop strategies to improve the vaccine-elicited T-cell activation towards MART-1.
528	15086273	Here we investigated the shuttle function of the HSP gp96 (glycoprotein 96) for a human melanoma peptide antigen MART-1 that was noncovalently bound to gp96 in vitro.
529	15149168	Peptide-specific CD8 T cells in PBLs were analyzed ex vivo using fluorescent HLA-A2/Melan-A multimers and IFN-gamma ELISPOT assays.
530	15149168	In vivo expansion of Melan-A-specific CD8 T cells was observed in 13 patients (1/12 after vaccination with peptide in AS02B and 12/17 after vaccination with peptide in IFA).
531	15149168	The T cells produced IFN-gamma and downregulated CD45RA and CD28.
532	15149168	We conclude that repeated vaccination with Melan-A peptide in IFA frequently leads to sustained responses of specific CD8 T cells that are detectable ex vivo and correlate with inflammatory skin reactions.
533	15149168	Peptide-specific CD8 T cells in PBLs were analyzed ex vivo using fluorescent HLA-A2/Melan-A multimers and IFN-gamma ELISPOT assays.
534	15149168	In vivo expansion of Melan-A-specific CD8 T cells was observed in 13 patients (1/12 after vaccination with peptide in AS02B and 12/17 after vaccination with peptide in IFA).
535	15149168	The T cells produced IFN-gamma and downregulated CD45RA and CD28.
536	15149168	We conclude that repeated vaccination with Melan-A peptide in IFA frequently leads to sustained responses of specific CD8 T cells that are detectable ex vivo and correlate with inflammatory skin reactions.
537	15149168	Peptide-specific CD8 T cells in PBLs were analyzed ex vivo using fluorescent HLA-A2/Melan-A multimers and IFN-gamma ELISPOT assays.
538	15149168	In vivo expansion of Melan-A-specific CD8 T cells was observed in 13 patients (1/12 after vaccination with peptide in AS02B and 12/17 after vaccination with peptide in IFA).
539	15149168	The T cells produced IFN-gamma and downregulated CD45RA and CD28.
540	15149168	We conclude that repeated vaccination with Melan-A peptide in IFA frequently leads to sustained responses of specific CD8 T cells that are detectable ex vivo and correlate with inflammatory skin reactions.
541	15235391	Ex vivo analysis of human antigen-specific CD8+ T-cell responses: quality assessment of fluorescent HLA-A2 multimer and interferon-gamma ELISPOT assays for patient immune monitoring.
542	15235391	The authors developed a standardized approach for immune monitoring of antigen-specific CD8+ T cells within peripheral blood lymphocytes (PBLs) that combines direct ex vivo analysis of Melan-A/MART-1 and influenza-specific CD8+ T cells with HLA-A2/peptide multimers and interferon-gamma ELISPOT assays.
543	15314544	In an open-label phase 2 trial, 10(7) autologous ex vivo generated DCs pulsed with the HLA-A*0201 immunodominant peptide MART-1(27-35) were administered to 10 subjects with stage II-IV melanoma.
544	15314544	Of four patients with measurable disease, one had stable disease for 6 months and another has a continued complete response for over 2 years, which is confounded by receiving a closely sequenced CTLA4 blocking antibody.
545	15314544	The DC vaccines induced determinant spreading in this subject, and CTLA4 blockade reactivated T cells with prior antigen exposure.
546	15314544	Sequential CTLA4 blockade may enhance the immune activity of DC-based immunotherapy.
547	15336780	Using tetramer staining and limiting dilution analyses as monitors of CTL responses, we found significant increases in the number of antigen-specific CTL in circulation after vaccination with the MART-1(27-35) peptide (AAGIGILTV)-pulsed autologous APC, the MAGE-1(161-169) peptide (EADPTGHSY)-pulsed APC, or with autologous tumor lysate-pulsed APC.
548	15336780	The decline in the CTL response was associated by a concomitant expansion of CD4(+) CD25(+)T cells.
549	15336780	Analysis of postvaccine peripheral blood lymphocytes (PBL) from patients showed an increased amount of interleukin (IL)-10 secretion on in vitro stimulation with IL-2 after successive vaccination.
550	15336780	Triple color flow cytometric analyses revealed cytoplasmic IL-10 in the CD4(+)CD25(+) T-cell fraction and the number of CD4(+)CD25(+) IL-10(+) T cells were found to increase significantly in postvaccine PBL.
551	15342370	We show that IFN-alpha and polyinosinic:polycytidylic acid (p-I:C) synergize with the "classical" type-1-polarizing cytokine cocktail [tumor necrosis factor alpha (TNFalpha)/IL-1beta/IFNgamma], allowing for serum-free generation of fully mature type-1-polarized DCs (DC1).
552	15342370	Such "alpha-type-1-polarized DC(s)" (alphaDC1) show high migratory responses to the CCR7 ligand, 6C-kine but produce much higher levels of IL-12p70 as compared to TNFalpha/IL-1beta/IL-6/prostaglandin E2 (PGE2)-matured DCs (sDC), the current "gold standard" in DC-based cancer vaccination.
553	15342370	A single round of in vitro sensitization with alphaDC1 (versus sDCs) induces up to 40-fold higher numbers of long-lived CTLs against melanoma-associated antigens: MART-1, gp100, and tyrosinase.
554	15384929	Eighteen of these patients also received vaccination with influenza (Flu), Melan-A (Mel), tyrosinase (Tyr), and NY-ESO-1 peptides.
555	15384929	FL induced increases in immature CD11c+ and CD123+ peripheral blood (PB) DCs.
556	15449035	The (MHC class I-restricted) peptides were from gp100, MART-1, tyrosinase, and MAGE-3.
557	15449035	The gp100 and MART-1 peptides had been modified to increase their immunogenicity.
558	15449035	The (MHC class I-restricted) peptides were from gp100, MART-1, tyrosinase, and MAGE-3.
559	15449035	The gp100 and MART-1 peptides had been modified to increase their immunogenicity.
560	15542372	We analyzed MART-1, S-100, MBP, and CD63 for melanoma and p53, MUC1, cyclin B1, HER-2/neu, and CEA for breast cancer.
561	15603192	Using five defined human T cell lines derived from melanoma patients, allogeneic DCs of HLA-A2, HLA-DR4 and HLA-DR7 haplotypes fused with MART-1, gp100, tyrosinase and TRP-2 expressing 888 mel melanoma cells were analysed for their ability to stimulate specific cytokine (IFN-gamma and GM-CSF) secretion.
562	15603192	DC-888 mel hybrids presented all tumour-associated epitopes to both CD4 and CD8 T cell lines in the context of MHC class II and I molecules, respectively.
563	15665624	We report on 10 patients with resected American Joint Committee on Cancer (AJCC)stage IIA-IIIC melanoma receiving individualized adjuvant peptide vaccinations derived from the melanosomal antigens MelanA/MART1, gp100 and tyrosinase, according to patient tumor associated HLA restricted antigen expression, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF).
564	15688403	We have comparatively evaluated the proliferative response of CTL induced in metastatic melanoma patients upon immunization against Melan-A/MART-1(27-35) tumor associated antigen (TAA) to IL-2, IL-7 or IL-15 cytokines, sharing a receptor common gamma-chain (c gamma-c cytokines).
565	15688403	All clones were able to kill tumor cell lines expressing HLA-A0201 and Melan-A/MART-1, and displayed phenotypic characteristics of effector/memory (CD45RA-/CCR7-) or CD45RA+/CCR7- effector cells in intermediate to late developmental stage (CD28-/CD276+/-) CTL.
566	15688403	Proliferative responses could be elicited or enhanced by IL-2 and IL-15, but not IL-7, in the absence or in the presence of T-cell receptor (TCR) triggering, respectively.
567	15688403	Accordingly, only IL-2 and IL-15 were able to promote the survival of the CTL clones under investigation.
568	15688403	CD8+ cells from one of the patients treated were obtained 6 months after the last vaccine boost and were cultured in the presence of Melan-A/MART-1(27-35) and each of the 3 cytokines under investigation.
569	15688403	Consistent with data from CTL clones, expansion of Melan-A/MART-1(27-35) tetramer positive cells was only observed in the presence of IL-2 or IL-15 but not IL-7.
570	15688403	Instead, when CD8+ cells from the same patient were sampled shortly (14 days) after an additional vaccination only IL-2 was able to promote the expansion of Melan-A/MART-1(27-35) tetramer positive cells.
571	15688403	We have comparatively evaluated the proliferative response of CTL induced in metastatic melanoma patients upon immunization against Melan-A/MART-1(27-35) tumor associated antigen (TAA) to IL-2, IL-7 or IL-15 cytokines, sharing a receptor common gamma-chain (c gamma-c cytokines).
572	15688403	All clones were able to kill tumor cell lines expressing HLA-A0201 and Melan-A/MART-1, and displayed phenotypic characteristics of effector/memory (CD45RA-/CCR7-) or CD45RA+/CCR7- effector cells in intermediate to late developmental stage (CD28-/CD276+/-) CTL.
573	15688403	Proliferative responses could be elicited or enhanced by IL-2 and IL-15, but not IL-7, in the absence or in the presence of T-cell receptor (TCR) triggering, respectively.
574	15688403	Accordingly, only IL-2 and IL-15 were able to promote the survival of the CTL clones under investigation.
575	15688403	CD8+ cells from one of the patients treated were obtained 6 months after the last vaccine boost and were cultured in the presence of Melan-A/MART-1(27-35) and each of the 3 cytokines under investigation.
576	15688403	Consistent with data from CTL clones, expansion of Melan-A/MART-1(27-35) tetramer positive cells was only observed in the presence of IL-2 or IL-15 but not IL-7.
577	15688403	Instead, when CD8+ cells from the same patient were sampled shortly (14 days) after an additional vaccination only IL-2 was able to promote the expansion of Melan-A/MART-1(27-35) tetramer positive cells.
578	15688403	We have comparatively evaluated the proliferative response of CTL induced in metastatic melanoma patients upon immunization against Melan-A/MART-1(27-35) tumor associated antigen (TAA) to IL-2, IL-7 or IL-15 cytokines, sharing a receptor common gamma-chain (c gamma-c cytokines).
579	15688403	All clones were able to kill tumor cell lines expressing HLA-A0201 and Melan-A/MART-1, and displayed phenotypic characteristics of effector/memory (CD45RA-/CCR7-) or CD45RA+/CCR7- effector cells in intermediate to late developmental stage (CD28-/CD276+/-) CTL.
580	15688403	Proliferative responses could be elicited or enhanced by IL-2 and IL-15, but not IL-7, in the absence or in the presence of T-cell receptor (TCR) triggering, respectively.
581	15688403	Accordingly, only IL-2 and IL-15 were able to promote the survival of the CTL clones under investigation.
582	15688403	CD8+ cells from one of the patients treated were obtained 6 months after the last vaccine boost and were cultured in the presence of Melan-A/MART-1(27-35) and each of the 3 cytokines under investigation.
583	15688403	Consistent with data from CTL clones, expansion of Melan-A/MART-1(27-35) tetramer positive cells was only observed in the presence of IL-2 or IL-15 but not IL-7.
584	15688403	Instead, when CD8+ cells from the same patient were sampled shortly (14 days) after an additional vaccination only IL-2 was able to promote the expansion of Melan-A/MART-1(27-35) tetramer positive cells.
585	15688403	We have comparatively evaluated the proliferative response of CTL induced in metastatic melanoma patients upon immunization against Melan-A/MART-1(27-35) tumor associated antigen (TAA) to IL-2, IL-7 or IL-15 cytokines, sharing a receptor common gamma-chain (c gamma-c cytokines).
586	15688403	All clones were able to kill tumor cell lines expressing HLA-A0201 and Melan-A/MART-1, and displayed phenotypic characteristics of effector/memory (CD45RA-/CCR7-) or CD45RA+/CCR7- effector cells in intermediate to late developmental stage (CD28-/CD276+/-) CTL.
587	15688403	Proliferative responses could be elicited or enhanced by IL-2 and IL-15, but not IL-7, in the absence or in the presence of T-cell receptor (TCR) triggering, respectively.
588	15688403	Accordingly, only IL-2 and IL-15 were able to promote the survival of the CTL clones under investigation.
589	15688403	CD8+ cells from one of the patients treated were obtained 6 months after the last vaccine boost and were cultured in the presence of Melan-A/MART-1(27-35) and each of the 3 cytokines under investigation.
590	15688403	Consistent with data from CTL clones, expansion of Melan-A/MART-1(27-35) tetramer positive cells was only observed in the presence of IL-2 or IL-15 but not IL-7.
591	15688403	Instead, when CD8+ cells from the same patient were sampled shortly (14 days) after an additional vaccination only IL-2 was able to promote the expansion of Melan-A/MART-1(27-35) tetramer positive cells.
592	15688403	We have comparatively evaluated the proliferative response of CTL induced in metastatic melanoma patients upon immunization against Melan-A/MART-1(27-35) tumor associated antigen (TAA) to IL-2, IL-7 or IL-15 cytokines, sharing a receptor common gamma-chain (c gamma-c cytokines).
593	15688403	All clones were able to kill tumor cell lines expressing HLA-A0201 and Melan-A/MART-1, and displayed phenotypic characteristics of effector/memory (CD45RA-/CCR7-) or CD45RA+/CCR7- effector cells in intermediate to late developmental stage (CD28-/CD276+/-) CTL.
594	15688403	Proliferative responses could be elicited or enhanced by IL-2 and IL-15, but not IL-7, in the absence or in the presence of T-cell receptor (TCR) triggering, respectively.
595	15688403	Accordingly, only IL-2 and IL-15 were able to promote the survival of the CTL clones under investigation.
596	15688403	CD8+ cells from one of the patients treated were obtained 6 months after the last vaccine boost and were cultured in the presence of Melan-A/MART-1(27-35) and each of the 3 cytokines under investigation.
597	15688403	Consistent with data from CTL clones, expansion of Melan-A/MART-1(27-35) tetramer positive cells was only observed in the presence of IL-2 or IL-15 but not IL-7.
598	15688403	Instead, when CD8+ cells from the same patient were sampled shortly (14 days) after an additional vaccination only IL-2 was able to promote the expansion of Melan-A/MART-1(27-35) tetramer positive cells.
599	15730392	Mature dendritic cells differentiated in the presence of interferon-beta and interleukin-3 prime functional antigen-specific CD8 T cells.
600	15730392	Monocytes incubated in the presence of interferon (IFN)-beta and interleukin (IL)-3 give rise to a distinct type of DCs (IFN-beta/IL-3 DCs) that are particularly efficient at eliciting IFN-gamma and IL-5 production by allogeneic helper T cells.
601	15730392	We assessed the capacity of this new type of DCs to prime antigen-specific naive CD8(+) T cells and compared them to the conventional DCs differentiated in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4 (GM-CSF/IL-4 DCs).
602	15730392	We demonstrate that IFN-beta/IL-3 DCs matured by TLR3 or CD40 ligation efficiently prime Melan-A(26-35)-specific CD8(+) T cells in vitro, at a similar level as GM-CSF/IL-4 DCs.
603	15730392	Activated antigen-specific CD8(+) T cells produced IFN-gamma and displayed potent cytotoxic activity against peptide-pulsed target cells.
604	15730392	Expansion of CD8(+) T cell numbers was generally higher following priming with CD40-L than with polyinosinic-polycytidylic acid (poly I:C) matured DCs.
605	15730392	These data indicate that IFN-beta/IL-3 DCs represent a promising cell population for the immunotherapy of cancer.
606	15755075	When well-characterized peptide epitopes are injected i.d., infiltrates of CD4+ and CD8+ T lymphocytes are frequently seen.
607	15755075	All patients received systemic Flt3 ligand (20 microg/kg/d) and i.d. peptides: Three NY-ESO-1 peptides, SLLMWITQCFL (157-167), SLLMWITQC (157-165), QLSLLMWIT (155-163); tyrosinase internal peptide YMDGTMSQV (368-376); Melan-A/MART-1 analogue peptide ELAGIGILTV (26-35, E27L substitution); and influenza matrix peptide GILGFVFTL (58-66).
608	15775996	Though the role of CD4 positive and CD8 positive cells in the immunological response to gene-modified DC has been well-characterized, the role of NK cells in this response has been somewhat less clear.
609	15775996	Immunization with MART-1 melanoma antigen-engineered DC in C57BL/6 mice resulted in the generation of antigen-specific cytotoxic T lymphocytes and in vivo protective responses to the murine B16 melanoma.
610	15775996	In conclusion, protective immunity after tumor antigen gene-modified DC immunization requires collaboration between CD4+ and CD8+ T cells and NK cells.
611	15812230	Nonreplicating recombinant vaccinia virus expressing CD40 ligand enhances APC capacity to stimulate specific CD4+ and CD8+ T cell responses.
612	15812230	Recently, we and others have demonstrated, in vitro and in vivo, that coexpression of CD80 and CD86 costimulatory molecules enhances the immunogenic capacity of a recombinant vaccinia virus (rVV) encoding different tumor-associated antigens.
613	15812230	To further investigate the capacity of these vectors to provide ligands for different costimulatory pathways relevant in the generation of T cell responses, we constructed a recombinant virus (rVV) expressing CD40 ligand or CD154 (CD154rVV).
614	15812230	Upon binding the CD40 receptor expressed on antigen presenting cells (APC), this molecule, physiologically expressed on activated CD4+ T cells, increases their antigen presentation and immunostimulatory capacities.
615	15812230	CD154rVV infection of autologous fibroblasts, monocytes, or iDC promoted the expression of a number of cytokines, including GM-CSF, TNF-alpha, and IL-15 in iDC.
616	15812230	Most importantly, IL-12 p40 gene expression and protein secretion were induced by CD154rVV but not by wild-type VV (WT VV) in either CD14+ cells or iDC, and these effects could be blocked by anti-CD40 monoclonal antibodies.
617	15812230	Furthermore, phenotypic characterization of CD154rVV infected iDC revealed enhanced expression of CD83 and CD86 surface markers as compared with wild-type vaccinia virus infection.
618	15812230	However, cytokine genes typically expressed by T cell receptor triggered T cells such as those encoding IL-2 and IFN-gamma, or T cell proliferation, were detectable to a significantly higher extent in CD154rVV infected cultures, as compared with WT VV.
619	15812230	Activation of specific CD8+ T cells was then investigated using MART-1/Melan-A(27-35) epitope as the model of tumor-associated antigen (TAA).
620	15824067	We found that only mature DCs (m-DC) but not immature DCs (im-DC) could be sufficiently loaded with exogenous class I-restricted peptides and were by far superior in expanding CD8(+) primary (Melan-A.A2 peptide-specific) and recall [Influenza matrix peptide (IMP) A2-specific] T cell responses.
621	15864589	Immunostimulatory properties of human dendritic cells generated using IFN-beta associated either with IL-3 or GM-CSF.
622	15864589	In the present study, we analyze the features of type I IFNs DC generated in the presence of either IL-3 (IL-3-DC) or GM-CSF (GM-CSF-DC) and compare their capacity to respond to poly(I:C) and to subsequently trigger T-cell activation.
623	15864589	After poly(I:C) maturation, both DC types display a marked upregulation of CD80, CD83 and CD86 and the same pattern of gene expression.
624	15864589	Priming of autologous T cells by IL-3-DC or GM-CSF-DC pulsed with an HLA-A2 restricted melan-A derived peptide, lead to the expansion of peptide specific CTL secreting high amounts of IFN-gamma.
625	15864589	We conclude that poly(I:C) matured IL-3-DC and GM-CSF-DC share similar phenotype and functional properties including the capacity to prime tumor-associated antigen specific CTL.
626	16037410	Dendritic cells differentiated in the presence of IFN-{beta} and IL-3 are potent inducers of an antigen-specific CD8+ T cell response.
627	16037410	Classically, mature monocyte-derived DC are generated in vitro in the presence of interleukin (IL)-4, granulocyte macrophage-colony stimulating factor, and inflammatory cytokines (G4-DC).
628	16037410	Recently, it has been described that DC can also be generated in the presence of IL-3 and interferon (IFN)-beta and that these DC are efficiently matured using polyriboinosinic polyribocytidylic acid (I3-DC).
629	16037410	Phenotypic characterization of the DC revealed differences in the expression of the monocyte marker CD14 and the maturation marker CD83.
630	16037410	Low expression of CD14 and high expression of CD83 characterized G4-DC, whereas I3-DC displayed intermediate expression of CD14 and CD83.
631	16037410	Upon CD40 ligation, G4-DC produced lower amounts of IFN-alpha and pulmonary and activation-regulated chemokine, similar amounts of IL-6, macrophage-inflammatory protein (MIP)-1alpha, and MIP-1beta, and higher amounts of IL-12 p70, tumor necrosis factor alpha, and MIP-3beta than I3-DC.
632	16037410	Finally, in vitro stimulations showed that fresh and frozen peptide-loaded I3-DC are more potent inducers of Melan-A-specific CD8(+) T cell responses than G4-DC.
633	16113607	Twenty-two HLA A*0201 patients with stage IV melanoma were enrolled in a phase 1 safety and feasibility trial using a composite dendritic cell (DC) vaccine generated by culturing CD34 hematopoietic progenitors and activated with IFN-alpha.
634	16113607	The DC vaccine was loaded with peptides derived from four melanoma tissue differentiation antigens (MART-1, tyrosinase, MAGE-3, and gp100) and influenza matrix peptide (Flu-MP).
635	16113607	Melanoma-peptide-specific recall memory CD8 T cells able to secrete IFN-gamma and to proliferate could be detected in six of the seven analyzed patients.
636	16165256	As a model epitope we chose L(27)Melan-A/Mart-1(26-35) HLA-A0201 restricted peptide from a melanoma-associated antigen widely used in tumor immunotherapy.
637	16216672	In human melanoma, we show here that MART-1(27-35)-specific CTLs generated with purified CD8+ cells survive and maintain their activity longer in culture than those CTLs generated by using total peripheral blood lymphocytes (PBL) taken either from patients or from normal donors.
638	16216672	For both normal donors or patients, polarization of PBL with Th1 conditioning with interleukin (IL)-12 (250 U/ml) and anti IL-4 antibody 1 mug/ml for 7 days before CTL generation, induced better and longer living CTL response and prevented the expansion of CD4+ T cells that have downregulatory activity.
639	16311731	Direct injection of a lentiviral vector encoding the melanoma antigen NY-ESO-1 in HLA-A2 transgenic mice primed NY-ESO-1-specific CD8+ cells that could be expanded by boosting with an NY-ESO-1 vaccinia virus.
640	16311731	In order to examine the priming step directly, we constructed another lentiviral vector expressing the melanoma antigen Melan-A (MART-1).
641	16331519	Between March 1999 and May 2000, 18 HLA-A*0201(+) patients with metastatic melanoma were enrolled in a phase I trial using a dendritic cell (DC) vaccine generated by culturing CD34(+) hematopoietic progenitors.
642	16331519	The DC vaccine was loaded with four melanoma peptides (MART-1/MelanA, tyrosinase, MAGE-3, and gp100), Influenza matrix peptide (Flu-MP), and keyhole limpet hemocyanin (KLH).
643	16353138	MelanA/MART-1-specific CD8+ T cells were expanded in 9/13 patients resulting in increased frequencies of memory cells in these patients.
644	16353138	CD8+ T cells acquired the capacity to secrete IFN-gamma, to proliferate in culture in response to the tumor antigen used for vaccination and postvaccine samples contained MelanA/MART-1-specific T cells that recognized also the natural MelanA/MART-1-antigen expressed by tumor cells.
645	16353138	MelanA/MART-1-specific CD8+ T cells were expanded in 9/13 patients resulting in increased frequencies of memory cells in these patients.
646	16353138	CD8+ T cells acquired the capacity to secrete IFN-gamma, to proliferate in culture in response to the tumor antigen used for vaccination and postvaccine samples contained MelanA/MART-1-specific T cells that recognized also the natural MelanA/MART-1-antigen expressed by tumor cells.
647	16424053	We compared the in vivo immunogenicity of the melanoma-associated antigen Melan-A(26-35) encoded by third-generation recombinant lentivector (rec. lv) or as peptide admixed with a strong adjuvant.
648	16424053	Ex vivo analyses of immunized HLA-A2/H-2K(b) mice showed that rec. lv triggered a stronger anti-Melan-A CD8+ T -cell response than peptide vaccine.
649	16424053	We compared the in vivo immunogenicity of the melanoma-associated antigen Melan-A(26-35) encoded by third-generation recombinant lentivector (rec. lv) or as peptide admixed with a strong adjuvant.
650	16424053	Ex vivo analyses of immunized HLA-A2/H-2K(b) mice showed that rec. lv triggered a stronger anti-Melan-A CD8+ T -cell response than peptide vaccine.
651	16468035	The ascites fluid contained the chemokines CCL10, CCL15, and CCL18 which was associated with a large influx of activated T cells, including CD8(+) T cells recognizing HLA-A2 tetramer complexes with peptides from Melan-A and NA17-A.
652	16468035	Although these defects were T cell intrinsic, we also observed abundant CD4(+)CD25(+)FoxP3(+) T cells, as well as transcripts for FoxP3, IL-10, PD-L1/B7-H1, and indoleamine-2,3-dioxygenase (IDO).
653	16567969	The melanoma differentiation antigens gp100, MART-1 and tyrosinase are involved in a common pathway of melanin synthesis.
654	16567969	The overall reactivities were 81.6% (gp100), 79.5% (MART-1), 59.6% (tyrosinase), 59.1% (77B), 60.7% (57B), 93.2% (S100) and 91.6% (SM5-1).
655	16567969	Co-ordinated loss was found for lesions negative for gp100 and MART-1 (9.4%, P < 0.0005), gp100 and tyrosinase (11.0%, P = 0.009), MART-1 and tyrosinase (15.2%, P < 0.0005) and gp100, MART-1 and tyrosinase (8.9%, P < 0.0005), which is up to six times higher than the expected calculated loss.
656	16567969	The melanoma differentiation antigens gp100, MART-1 and tyrosinase are involved in a common pathway of melanin synthesis.
657	16567969	The overall reactivities were 81.6% (gp100), 79.5% (MART-1), 59.6% (tyrosinase), 59.1% (77B), 60.7% (57B), 93.2% (S100) and 91.6% (SM5-1).
658	16567969	Co-ordinated loss was found for lesions negative for gp100 and MART-1 (9.4%, P < 0.0005), gp100 and tyrosinase (11.0%, P = 0.009), MART-1 and tyrosinase (15.2%, P < 0.0005) and gp100, MART-1 and tyrosinase (8.9%, P < 0.0005), which is up to six times higher than the expected calculated loss.
659	16567969	The melanoma differentiation antigens gp100, MART-1 and tyrosinase are involved in a common pathway of melanin synthesis.
660	16567969	The overall reactivities were 81.6% (gp100), 79.5% (MART-1), 59.6% (tyrosinase), 59.1% (77B), 60.7% (57B), 93.2% (S100) and 91.6% (SM5-1).
661	16567969	Co-ordinated loss was found for lesions negative for gp100 and MART-1 (9.4%, P < 0.0005), gp100 and tyrosinase (11.0%, P = 0.009), MART-1 and tyrosinase (15.2%, P < 0.0005) and gp100, MART-1 and tyrosinase (8.9%, P < 0.0005), which is up to six times higher than the expected calculated loss.
662	16618772	We found that soluble human LAG-3 significantly sustained the generation and expansion of influenza matrix protein Melan-A/MART-1 and survivin-specific CD8+ T lymphocytes in peripheral blood mononuclear cells (PBMC) of both cancer patients and healthy donors, showing its ability to boost CD8+ T-cell memory response or to prime naive T cells in vitro.
663	16651452	Immunization of stage IV melanoma patients with Melan-A/MART-1 and gp100 peptides plus IFN-alpha results in the activation of specific CD8(+) T cells and monocyte/dendritic cell precursors.
664	16651452	We have carried out a pilot phase I-II trial to determine the effects of IFN-alpha, administered as an adjuvant of Melan-A/MART-1:26-35(27L) and gp100:209-217(210M) peptides, on immune responses in stage IV melanoma patients.
665	16651452	In five of the seven evaluable patients, a consistent enhancement of CD8(+) T cells recognizing modified and native MART-1 and gp100 peptides and MART-1(+)gp100(+) melanoma cells was observed.
666	16651452	In all patients, treatment augmented significantly the percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell fraction.
667	16651452	An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed.
668	16651452	Notably, postvaccination monocytes from two of the three patients showing stable disease or long disease-free survival showed an enhanced antigen-presenting cell function and capability to secrete IP10/CXCL10 when tested in mixed leukocyte reaction assays, associated to a boost of antigen and melanoma-specific CD8(+) T cells.
669	16651452	Immunization of stage IV melanoma patients with Melan-A/MART-1 and gp100 peptides plus IFN-alpha results in the activation of specific CD8(+) T cells and monocyte/dendritic cell precursors.
670	16651452	We have carried out a pilot phase I-II trial to determine the effects of IFN-alpha, administered as an adjuvant of Melan-A/MART-1:26-35(27L) and gp100:209-217(210M) peptides, on immune responses in stage IV melanoma patients.
671	16651452	In five of the seven evaluable patients, a consistent enhancement of CD8(+) T cells recognizing modified and native MART-1 and gp100 peptides and MART-1(+)gp100(+) melanoma cells was observed.
672	16651452	In all patients, treatment augmented significantly the percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell fraction.
673	16651452	An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed.
674	16651452	Notably, postvaccination monocytes from two of the three patients showing stable disease or long disease-free survival showed an enhanced antigen-presenting cell function and capability to secrete IP10/CXCL10 when tested in mixed leukocyte reaction assays, associated to a boost of antigen and melanoma-specific CD8(+) T cells.
675	16651452	Immunization of stage IV melanoma patients with Melan-A/MART-1 and gp100 peptides plus IFN-alpha results in the activation of specific CD8(+) T cells and monocyte/dendritic cell precursors.
676	16651452	We have carried out a pilot phase I-II trial to determine the effects of IFN-alpha, administered as an adjuvant of Melan-A/MART-1:26-35(27L) and gp100:209-217(210M) peptides, on immune responses in stage IV melanoma patients.
677	16651452	In five of the seven evaluable patients, a consistent enhancement of CD8(+) T cells recognizing modified and native MART-1 and gp100 peptides and MART-1(+)gp100(+) melanoma cells was observed.
678	16651452	In all patients, treatment augmented significantly the percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell fraction.
679	16651452	An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed.
680	16651452	Notably, postvaccination monocytes from two of the three patients showing stable disease or long disease-free survival showed an enhanced antigen-presenting cell function and capability to secrete IP10/CXCL10 when tested in mixed leukocyte reaction assays, associated to a boost of antigen and melanoma-specific CD8(+) T cells.
681	16709813	In HLA-A2 individuals, the CD8 T cell response against the differentiation Ag Melan-A is mainly directed toward the peptide Melan-A26-35.
682	16709813	Based on these findings, we compared the CD8 T cell response to human and murine Melan-A peptide by immunizing HLA-A2 transgenic mice.
683	16709813	In HLA-A2 individuals, the CD8 T cell response against the differentiation Ag Melan-A is mainly directed toward the peptide Melan-A26-35.
684	16709813	Based on these findings, we compared the CD8 T cell response to human and murine Melan-A peptide by immunizing HLA-A2 transgenic mice.
685	16761313	Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide.
686	16761313	To shed light on the cross-reactive potential of vaccine-induced cells, we analyzed the reactivity of CD8(+) T cells following vaccination of HLA-A2(+) melanoma patients with Melan-A peptide, incomplete Freund's adjuvant and CpG-oligodeoxynucleotide adjuvant, which was shown to induce strong expansion of Melan-A-reactive CD8(+) T cells in vivo.
687	16761313	A collection of predicted Melan-A cross-reactive peptides, identified from a combinatorial peptide library, was used to probe functional antigen recognition of PBMC ex vivo and Melan-A-reactive CD8(+) T cell clones.
688	16761313	While Melan-A-reactive CD8(+) T cells prior to vaccination are usually constituted of widely cross-reactive naive cells, we show that peptide vaccination resulted in expansion of memory T cells displaying a reactivity predominantly restricted to the antigen of interest.
689	16761313	Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide.
690	16761313	To shed light on the cross-reactive potential of vaccine-induced cells, we analyzed the reactivity of CD8(+) T cells following vaccination of HLA-A2(+) melanoma patients with Melan-A peptide, incomplete Freund's adjuvant and CpG-oligodeoxynucleotide adjuvant, which was shown to induce strong expansion of Melan-A-reactive CD8(+) T cells in vivo.
691	16761313	A collection of predicted Melan-A cross-reactive peptides, identified from a combinatorial peptide library, was used to probe functional antigen recognition of PBMC ex vivo and Melan-A-reactive CD8(+) T cell clones.
692	16761313	While Melan-A-reactive CD8(+) T cells prior to vaccination are usually constituted of widely cross-reactive naive cells, we show that peptide vaccination resulted in expansion of memory T cells displaying a reactivity predominantly restricted to the antigen of interest.
693	16761313	Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide.
694	16761313	To shed light on the cross-reactive potential of vaccine-induced cells, we analyzed the reactivity of CD8(+) T cells following vaccination of HLA-A2(+) melanoma patients with Melan-A peptide, incomplete Freund's adjuvant and CpG-oligodeoxynucleotide adjuvant, which was shown to induce strong expansion of Melan-A-reactive CD8(+) T cells in vivo.
695	16761313	A collection of predicted Melan-A cross-reactive peptides, identified from a combinatorial peptide library, was used to probe functional antigen recognition of PBMC ex vivo and Melan-A-reactive CD8(+) T cell clones.
696	16761313	While Melan-A-reactive CD8(+) T cells prior to vaccination are usually constituted of widely cross-reactive naive cells, we show that peptide vaccination resulted in expansion of memory T cells displaying a reactivity predominantly restricted to the antigen of interest.
697	16761313	Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide.
698	16761313	To shed light on the cross-reactive potential of vaccine-induced cells, we analyzed the reactivity of CD8(+) T cells following vaccination of HLA-A2(+) melanoma patients with Melan-A peptide, incomplete Freund's adjuvant and CpG-oligodeoxynucleotide adjuvant, which was shown to induce strong expansion of Melan-A-reactive CD8(+) T cells in vivo.
699	16761313	A collection of predicted Melan-A cross-reactive peptides, identified from a combinatorial peptide library, was used to probe functional antigen recognition of PBMC ex vivo and Melan-A-reactive CD8(+) T cell clones.
700	16761313	While Melan-A-reactive CD8(+) T cells prior to vaccination are usually constituted of widely cross-reactive naive cells, we show that peptide vaccination resulted in expansion of memory T cells displaying a reactivity predominantly restricted to the antigen of interest.
701	16818795	In this study, using a novel ex vivo molecular-based approach at the single-cell level, we identified a single, naturally primed T cell clone that dominated the human CD8(+) T cell response to the Melan-A/MART-1 Ag.
702	16845331	Although staining for S100 protein is generally positive, staining for other melanoma differentiation antigens, particularly gp100, Melan-A/MART1 and tyrosinase, is often negative despite being commonly positive in other melanoma types.
703	16845331	We characterized the patterns of antigen expression of desmoplastic melanoma from 32 patients, including gp100, Melan-A/MART-1, tyrosinase, MAGE-A1, MAGE-A4 and NY-ESO-1.
704	16845331	Although staining for S100 protein is generally positive, staining for other melanoma differentiation antigens, particularly gp100, Melan-A/MART1 and tyrosinase, is often negative despite being commonly positive in other melanoma types.
705	16845331	We characterized the patterns of antigen expression of desmoplastic melanoma from 32 patients, including gp100, Melan-A/MART-1, tyrosinase, MAGE-A1, MAGE-A4 and NY-ESO-1.
706	16849476	In the present study, ex vivo analyses of Melan-A-specific CD8(+) T cells following vaccination with Melan-A peptide and CpG oligodeoxynucleotides revealed the successful induction in the circulation of effective melanoma-specific T cells, i.e., with phenotypic and functional characteristics similar to those of CTL specific for immunodominant viral Ags.
707	16918131	Autologous DCs were generated in vitro from peripheral blood monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4).
708	16918131	DCs were pulsed with melanoma cell lysate from a cloned and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100.
709	16971810	Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity.
710	16971810	DCs were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (granulocyte macrophage-colony stimulating factor) and interleukin (IL-4) and activated by additional culture with tumor necrosis factor and CD40 ligand.
711	16971810	Three out of 13 analyzed patients showed T-cell immunity to melanoma antigen recognized by autologous T cells (MART-1) tissue differentiation antigen.
712	16971810	Two of 3 patients showed improved immune function after vaccinations demonstrated by improved secretion of interferon (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides.
713	16971810	In one of these patients, vaccination led to elicitation of CD8 T-cell immunity specific to a novel peptide-derived from MART-1 antigen, suggesting that cross-priming/presentation of melanoma antigens by DC vaccine had occurred.
714	16971810	Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity.
715	16971810	DCs were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (granulocyte macrophage-colony stimulating factor) and interleukin (IL-4) and activated by additional culture with tumor necrosis factor and CD40 ligand.
716	16971810	Three out of 13 analyzed patients showed T-cell immunity to melanoma antigen recognized by autologous T cells (MART-1) tissue differentiation antigen.
717	16971810	Two of 3 patients showed improved immune function after vaccinations demonstrated by improved secretion of interferon (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides.
718	16971810	In one of these patients, vaccination led to elicitation of CD8 T-cell immunity specific to a novel peptide-derived from MART-1 antigen, suggesting that cross-priming/presentation of melanoma antigens by DC vaccine had occurred.
719	16971810	Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity.
720	16971810	DCs were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (granulocyte macrophage-colony stimulating factor) and interleukin (IL-4) and activated by additional culture with tumor necrosis factor and CD40 ligand.
721	16971810	Three out of 13 analyzed patients showed T-cell immunity to melanoma antigen recognized by autologous T cells (MART-1) tissue differentiation antigen.
722	16971810	Two of 3 patients showed improved immune function after vaccinations demonstrated by improved secretion of interferon (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides.
723	16971810	In one of these patients, vaccination led to elicitation of CD8 T-cell immunity specific to a novel peptide-derived from MART-1 antigen, suggesting that cross-priming/presentation of melanoma antigens by DC vaccine had occurred.
724	16971810	Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity.
725	16971810	DCs were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (granulocyte macrophage-colony stimulating factor) and interleukin (IL-4) and activated by additional culture with tumor necrosis factor and CD40 ligand.
726	16971810	Three out of 13 analyzed patients showed T-cell immunity to melanoma antigen recognized by autologous T cells (MART-1) tissue differentiation antigen.
727	16971810	Two of 3 patients showed improved immune function after vaccinations demonstrated by improved secretion of interferon (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides.
728	16971810	In one of these patients, vaccination led to elicitation of CD8 T-cell immunity specific to a novel peptide-derived from MART-1 antigen, suggesting that cross-priming/presentation of melanoma antigens by DC vaccine had occurred.
729	17082590	Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.
730	17082590	In this study, we describe two novel Melan-A/MART-1-derived sequences recognized by CD4 T cells from melanoma patients.
731	17082590	These epitopes can be mimicked by peptides Melan-A27-40 presented by HLA-DRB1*0101 and HLA-DRB1*0102 and Melan-A25-36 presented by HLA-DQB1*0602 and HLA-DRB1*0301.
732	17082590	CD4 T cell clones specific for these epitopes recognize Melan-A/MART-1+ tumor cells and Melan-A/MART-1-transduced EBV-B cells and recognition is reduced by inhibitors of the MHC class II presentation pathway.
733	17082590	Moreover, Melan-A-specific Abs could be detected in the serum of patients with measurable CD4 T cell responses specific for Melan-A/MART-1.
734	17082590	Interestingly, even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients.
735	17082590	Using Melan-A/MART-1(25-36)/DQ6 tetramers, we could detect Ag-specific CD4 T cells directly ex vivo in circulating lymphocytes of a melanoma patient.
736	17082590	Together, these results provide the basis for monitoring of naturally occurring and vaccine-induced Melan-A/MART-1-specific CD4 T cell responses, allowing precise and ex vivo characterization of responding T cells.
737	17082590	Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.
738	17082590	In this study, we describe two novel Melan-A/MART-1-derived sequences recognized by CD4 T cells from melanoma patients.
739	17082590	These epitopes can be mimicked by peptides Melan-A27-40 presented by HLA-DRB1*0101 and HLA-DRB1*0102 and Melan-A25-36 presented by HLA-DQB1*0602 and HLA-DRB1*0301.
740	17082590	CD4 T cell clones specific for these epitopes recognize Melan-A/MART-1+ tumor cells and Melan-A/MART-1-transduced EBV-B cells and recognition is reduced by inhibitors of the MHC class II presentation pathway.
741	17082590	Moreover, Melan-A-specific Abs could be detected in the serum of patients with measurable CD4 T cell responses specific for Melan-A/MART-1.
742	17082590	Interestingly, even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients.
743	17082590	Using Melan-A/MART-1(25-36)/DQ6 tetramers, we could detect Ag-specific CD4 T cells directly ex vivo in circulating lymphocytes of a melanoma patient.
744	17082590	Together, these results provide the basis for monitoring of naturally occurring and vaccine-induced Melan-A/MART-1-specific CD4 T cell responses, allowing precise and ex vivo characterization of responding T cells.
745	17082590	Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.
746	17082590	In this study, we describe two novel Melan-A/MART-1-derived sequences recognized by CD4 T cells from melanoma patients.
747	17082590	These epitopes can be mimicked by peptides Melan-A27-40 presented by HLA-DRB1*0101 and HLA-DRB1*0102 and Melan-A25-36 presented by HLA-DQB1*0602 and HLA-DRB1*0301.
748	17082590	CD4 T cell clones specific for these epitopes recognize Melan-A/MART-1+ tumor cells and Melan-A/MART-1-transduced EBV-B cells and recognition is reduced by inhibitors of the MHC class II presentation pathway.
749	17082590	Moreover, Melan-A-specific Abs could be detected in the serum of patients with measurable CD4 T cell responses specific for Melan-A/MART-1.
750	17082590	Interestingly, even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients.
751	17082590	Using Melan-A/MART-1(25-36)/DQ6 tetramers, we could detect Ag-specific CD4 T cells directly ex vivo in circulating lymphocytes of a melanoma patient.
752	17082590	Together, these results provide the basis for monitoring of naturally occurring and vaccine-induced Melan-A/MART-1-specific CD4 T cell responses, allowing precise and ex vivo characterization of responding T cells.
753	17082590	Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.
754	17082590	In this study, we describe two novel Melan-A/MART-1-derived sequences recognized by CD4 T cells from melanoma patients.
755	17082590	These epitopes can be mimicked by peptides Melan-A27-40 presented by HLA-DRB1*0101 and HLA-DRB1*0102 and Melan-A25-36 presented by HLA-DQB1*0602 and HLA-DRB1*0301.
756	17082590	CD4 T cell clones specific for these epitopes recognize Melan-A/MART-1+ tumor cells and Melan-A/MART-1-transduced EBV-B cells and recognition is reduced by inhibitors of the MHC class II presentation pathway.
757	17082590	Moreover, Melan-A-specific Abs could be detected in the serum of patients with measurable CD4 T cell responses specific for Melan-A/MART-1.
758	17082590	Interestingly, even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients.
759	17082590	Using Melan-A/MART-1(25-36)/DQ6 tetramers, we could detect Ag-specific CD4 T cells directly ex vivo in circulating lymphocytes of a melanoma patient.
760	17082590	Together, these results provide the basis for monitoring of naturally occurring and vaccine-induced Melan-A/MART-1-specific CD4 T cell responses, allowing precise and ex vivo characterization of responding T cells.
761	17082590	Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.
762	17082590	In this study, we describe two novel Melan-A/MART-1-derived sequences recognized by CD4 T cells from melanoma patients.
763	17082590	These epitopes can be mimicked by peptides Melan-A27-40 presented by HLA-DRB1*0101 and HLA-DRB1*0102 and Melan-A25-36 presented by HLA-DQB1*0602 and HLA-DRB1*0301.
764	17082590	CD4 T cell clones specific for these epitopes recognize Melan-A/MART-1+ tumor cells and Melan-A/MART-1-transduced EBV-B cells and recognition is reduced by inhibitors of the MHC class II presentation pathway.
765	17082590	Moreover, Melan-A-specific Abs could be detected in the serum of patients with measurable CD4 T cell responses specific for Melan-A/MART-1.
766	17082590	Interestingly, even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients.
767	17082590	Using Melan-A/MART-1(25-36)/DQ6 tetramers, we could detect Ag-specific CD4 T cells directly ex vivo in circulating lymphocytes of a melanoma patient.
768	17082590	Together, these results provide the basis for monitoring of naturally occurring and vaccine-induced Melan-A/MART-1-specific CD4 T cell responses, allowing precise and ex vivo characterization of responding T cells.
769	17082590	Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.
770	17082590	In this study, we describe two novel Melan-A/MART-1-derived sequences recognized by CD4 T cells from melanoma patients.
771	17082590	These epitopes can be mimicked by peptides Melan-A27-40 presented by HLA-DRB1*0101 and HLA-DRB1*0102 and Melan-A25-36 presented by HLA-DQB1*0602 and HLA-DRB1*0301.
772	17082590	CD4 T cell clones specific for these epitopes recognize Melan-A/MART-1+ tumor cells and Melan-A/MART-1-transduced EBV-B cells and recognition is reduced by inhibitors of the MHC class II presentation pathway.
773	17082590	Moreover, Melan-A-specific Abs could be detected in the serum of patients with measurable CD4 T cell responses specific for Melan-A/MART-1.
774	17082590	Interestingly, even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients.
775	17082590	Using Melan-A/MART-1(25-36)/DQ6 tetramers, we could detect Ag-specific CD4 T cells directly ex vivo in circulating lymphocytes of a melanoma patient.
776	17082590	Together, these results provide the basis for monitoring of naturally occurring and vaccine-induced Melan-A/MART-1-specific CD4 T cell responses, allowing precise and ex vivo characterization of responding T cells.
777	17082590	Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.
778	17082590	In this study, we describe two novel Melan-A/MART-1-derived sequences recognized by CD4 T cells from melanoma patients.
779	17082590	These epitopes can be mimicked by peptides Melan-A27-40 presented by HLA-DRB1*0101 and HLA-DRB1*0102 and Melan-A25-36 presented by HLA-DQB1*0602 and HLA-DRB1*0301.
780	17082590	CD4 T cell clones specific for these epitopes recognize Melan-A/MART-1+ tumor cells and Melan-A/MART-1-transduced EBV-B cells and recognition is reduced by inhibitors of the MHC class II presentation pathway.
781	17082590	Moreover, Melan-A-specific Abs could be detected in the serum of patients with measurable CD4 T cell responses specific for Melan-A/MART-1.
782	17082590	Interestingly, even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients.
783	17082590	Using Melan-A/MART-1(25-36)/DQ6 tetramers, we could detect Ag-specific CD4 T cells directly ex vivo in circulating lymphocytes of a melanoma patient.
784	17082590	Together, these results provide the basis for monitoring of naturally occurring and vaccine-induced Melan-A/MART-1-specific CD4 T cell responses, allowing precise and ex vivo characterization of responding T cells.
785	17318652	A HLA-DQ5 restricted Melan-A/MART-1 epitope presented by melanoma tumor cells to CD4+ T lymphocytes.
786	17318652	Here we describe a new Melan-A/MART-1 epitope recognized in the context of HLA-DQa1*0101 and HLA-DQb1*0501, -DQb1*0502 or -DQb1*0504 molecules by a CD4+ T cell clone.
787	17318652	Importantly, this clone specifically recognizes and kills tumor cell lines expressing Melan-A and either HLA-DQb1*0501, -DQb1*0504 or -DQb1*0502 molecules.
788	17318652	Moreover, we could detect CD4+ T cells secreting IFN-gamma in response to Melan-A51-63 and Melan-A51-73 peptides among tumor infiltrating and blood lymphocytes from HLA-DQ5+ patients.
789	17318652	A HLA-DQ5 restricted Melan-A/MART-1 epitope presented by melanoma tumor cells to CD4+ T lymphocytes.
790	17318652	Here we describe a new Melan-A/MART-1 epitope recognized in the context of HLA-DQa1*0101 and HLA-DQb1*0501, -DQb1*0502 or -DQb1*0504 molecules by a CD4+ T cell clone.
791	17318652	Importantly, this clone specifically recognizes and kills tumor cell lines expressing Melan-A and either HLA-DQb1*0501, -DQb1*0504 or -DQb1*0502 molecules.
792	17318652	Moreover, we could detect CD4+ T cells secreting IFN-gamma in response to Melan-A51-63 and Melan-A51-73 peptides among tumor infiltrating and blood lymphocytes from HLA-DQ5+ patients.
793	17318652	A HLA-DQ5 restricted Melan-A/MART-1 epitope presented by melanoma tumor cells to CD4+ T lymphocytes.
794	17318652	Here we describe a new Melan-A/MART-1 epitope recognized in the context of HLA-DQa1*0101 and HLA-DQb1*0501, -DQb1*0502 or -DQb1*0504 molecules by a CD4+ T cell clone.
795	17318652	Importantly, this clone specifically recognizes and kills tumor cell lines expressing Melan-A and either HLA-DQb1*0501, -DQb1*0504 or -DQb1*0502 molecules.
796	17318652	Moreover, we could detect CD4+ T cells secreting IFN-gamma in response to Melan-A51-63 and Melan-A51-73 peptides among tumor infiltrating and blood lymphocytes from HLA-DQ5+ patients.
797	17375074	We programmed mouse bone marrow (BM) cells with lentiviral vectors (LV-GI4) so that they produced granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in an autonomous manner.
798	17375074	The immunostimulatory efficacy of DC/LV-GI4 cells was evaluated using MART1 and TRP2 as co-expressed melanoma antigens.
799	17376215	Adjuvant immunohistological markers are the calcium-binding protein S-100, the melanoma antigen HMB-45, the melanoma-expressed protein Melan A, and microphthalmia-associated transcription factor (MiTF).
800	17589432	Synthetic melanoma-associated antigen MART1 mRNA was formulated with a polyethylene glycol (PEG)ylated derivative of histidylated polylysine and L-histidine-(N,N-di-n-hexadecylamine)ethylamide liposomes (termed histidylated lipopolyplexes).
801	17589432	MART1 mRNA lipopolyplexes elicited a cellular immune response characterized by the production of interferon-gamma and the induction of cytotoxic T lymphocytes.
802	17589432	Finally, the anti-B16 response was enhanced using a formulation containing both MART1 mRNA and MART1-LAMP1 mRNA encoding the antigen targeted to the major histocompatibility complex class II compartments by the lysosomal sorting signal of LAMP1 protein.
803	17589432	Synthetic melanoma-associated antigen MART1 mRNA was formulated with a polyethylene glycol (PEG)ylated derivative of histidylated polylysine and L-histidine-(N,N-di-n-hexadecylamine)ethylamide liposomes (termed histidylated lipopolyplexes).
804	17589432	MART1 mRNA lipopolyplexes elicited a cellular immune response characterized by the production of interferon-gamma and the induction of cytotoxic T lymphocytes.
805	17589432	Finally, the anti-B16 response was enhanced using a formulation containing both MART1 mRNA and MART1-LAMP1 mRNA encoding the antigen targeted to the major histocompatibility complex class II compartments by the lysosomal sorting signal of LAMP1 protein.
806	17589432	Synthetic melanoma-associated antigen MART1 mRNA was formulated with a polyethylene glycol (PEG)ylated derivative of histidylated polylysine and L-histidine-(N,N-di-n-hexadecylamine)ethylamide liposomes (termed histidylated lipopolyplexes).
807	17589432	MART1 mRNA lipopolyplexes elicited a cellular immune response characterized by the production of interferon-gamma and the induction of cytotoxic T lymphocytes.
808	17589432	Finally, the anti-B16 response was enhanced using a formulation containing both MART1 mRNA and MART1-LAMP1 mRNA encoding the antigen targeted to the major histocompatibility complex class II compartments by the lysosomal sorting signal of LAMP1 protein.
809	17898045	In this study, we examined the effects of a fully human PD-1-abrogating antibody on the in vitro expansion and function of human vaccine-induced CD8+ T cells (CTLs) specific for the melanoma-associated antigens glycoprotein 100 (gp100) and melanoma antigen recognized by T cells (MART)-1.
810	17898045	PD-1 blockade during peptide stimulation augmented the absolute numbers of CD3+, CD4+, CD8+ and gp100/MART-1 MHC:peptide tetramer+ CTLs.
811	17898045	This correlated with increased frequencies of IFN-gamma-secreting antigen-specific cells and augmented lysis of gp100+/MART-1+ melanoma targets.
812	17898045	In this study, we examined the effects of a fully human PD-1-abrogating antibody on the in vitro expansion and function of human vaccine-induced CD8+ T cells (CTLs) specific for the melanoma-associated antigens glycoprotein 100 (gp100) and melanoma antigen recognized by T cells (MART)-1.
813	17898045	PD-1 blockade during peptide stimulation augmented the absolute numbers of CD3+, CD4+, CD8+ and gp100/MART-1 MHC:peptide tetramer+ CTLs.
814	17898045	This correlated with increased frequencies of IFN-gamma-secreting antigen-specific cells and augmented lysis of gp100+/MART-1+ melanoma targets.
815	17898045	In this study, we examined the effects of a fully human PD-1-abrogating antibody on the in vitro expansion and function of human vaccine-induced CD8+ T cells (CTLs) specific for the melanoma-associated antigens glycoprotein 100 (gp100) and melanoma antigen recognized by T cells (MART)-1.
816	17898045	PD-1 blockade during peptide stimulation augmented the absolute numbers of CD3+, CD4+, CD8+ and gp100/MART-1 MHC:peptide tetramer+ CTLs.
817	17898045	This correlated with increased frequencies of IFN-gamma-secreting antigen-specific cells and augmented lysis of gp100+/MART-1+ melanoma targets.
818	18097665	A HLA-Cw*0701 restricted Melan-A/MART1 epitope presented by melanoma tumor cells to CD8+ tumor infiltrating lymphocytes.
819	18097665	Melan-A/MART1 is a melanocytic differentiation antigen recognized on melanoma tumor cells by CD8+ and CD4+ T cells.
820	18097665	In this study, we describe a new epitope of this protein recognized in the context of HLA-Cw*0701 molecules by a CD8+ tumor infiltrating lymphocyte (TIL) clone.
821	18097665	This CD8+ TIL clone specifically recognized and killed a fraction of melanoma cells lines expressing Melan-A/MART1 and HLA-Cw*0701.
822	18097665	A HLA-Cw*0701 restricted Melan-A/MART1 epitope presented by melanoma tumor cells to CD8+ tumor infiltrating lymphocytes.
823	18097665	Melan-A/MART1 is a melanocytic differentiation antigen recognized on melanoma tumor cells by CD8+ and CD4+ T cells.
824	18097665	In this study, we describe a new epitope of this protein recognized in the context of HLA-Cw*0701 molecules by a CD8+ tumor infiltrating lymphocyte (TIL) clone.
825	18097665	This CD8+ TIL clone specifically recognized and killed a fraction of melanoma cells lines expressing Melan-A/MART1 and HLA-Cw*0701.
826	18097665	A HLA-Cw*0701 restricted Melan-A/MART1 epitope presented by melanoma tumor cells to CD8+ tumor infiltrating lymphocytes.
827	18097665	Melan-A/MART1 is a melanocytic differentiation antigen recognized on melanoma tumor cells by CD8+ and CD4+ T cells.
828	18097665	In this study, we describe a new epitope of this protein recognized in the context of HLA-Cw*0701 molecules by a CD8+ tumor infiltrating lymphocyte (TIL) clone.
829	18097665	This CD8+ TIL clone specifically recognized and killed a fraction of melanoma cells lines expressing Melan-A/MART1 and HLA-Cw*0701.
830	18156189	MART-1-modified peptide (A27L peptide) and apoptotic HLA-A*0201-positive, MART-1-positive JCOCB tumor cell lines were used as tumor antigen sources.
831	18157012	We used the transfer of RNAs encoding the well-defined melanoma TAAs tyrosinase, Melan-A, CDK4mut, gp100, SNRP116mut, and GPNMBmut to characterize DCs at the levels of transfected RNA, expressed protein and peptide-major histocompatibility complex ligand presentation.
832	18317358	We performed a phase 1/2 trial testing the safety, toxicity, and immune response of a vaccine consisting of autologous dendritic cells (DCs) transduced with a replication-defective adenovirus (AdV) encoding the full-length melanoma antigen MART-1/Melan-A (MART-1).
833	18317358	This vaccine was designed to activate MART-1-specific CD+8 and CD4+ T cells.
834	18317358	CD8+ T-cell responses to MART-1 27-35 were assessed by both major histocompatibility complex class I tetramer and interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) before, during, and after each vaccine and CD4+ T-cell responses to MART-1 51-73 were followed by IFN-gamma ELISPOT.
835	18317358	Determinant spreading from the immunizing antigen MART-1 to other melanoma antigens [gp100, tyrosinase, human melanoma antigen-A3 (MAGE-A3)] was assessed by IFN-gamma ELISPOT.
836	18317358	Significant CD8+ and/or CD4+ MART-1-specific T-cell responses were observed in 6/11 and 2/4 patients evaluated, respectively, indicating that the E1-deleted adenovirus encoding the cDNA for MART-1/Melan-A (AdVMART1)/DC vaccine activated both helper and killer T cells in vivo.
837	18317358	Responses in CD8+ and CD4+ T cells to additional antigens were noted in 2 patients.
838	18317358	We performed a phase 1/2 trial testing the safety, toxicity, and immune response of a vaccine consisting of autologous dendritic cells (DCs) transduced with a replication-defective adenovirus (AdV) encoding the full-length melanoma antigen MART-1/Melan-A (MART-1).
839	18317358	This vaccine was designed to activate MART-1-specific CD+8 and CD4+ T cells.
840	18317358	CD8+ T-cell responses to MART-1 27-35 were assessed by both major histocompatibility complex class I tetramer and interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) before, during, and after each vaccine and CD4+ T-cell responses to MART-1 51-73 were followed by IFN-gamma ELISPOT.
841	18317358	Determinant spreading from the immunizing antigen MART-1 to other melanoma antigens [gp100, tyrosinase, human melanoma antigen-A3 (MAGE-A3)] was assessed by IFN-gamma ELISPOT.
842	18317358	Significant CD8+ and/or CD4+ MART-1-specific T-cell responses were observed in 6/11 and 2/4 patients evaluated, respectively, indicating that the E1-deleted adenovirus encoding the cDNA for MART-1/Melan-A (AdVMART1)/DC vaccine activated both helper and killer T cells in vivo.
843	18317358	Responses in CD8+ and CD4+ T cells to additional antigens were noted in 2 patients.
844	18317358	We performed a phase 1/2 trial testing the safety, toxicity, and immune response of a vaccine consisting of autologous dendritic cells (DCs) transduced with a replication-defective adenovirus (AdV) encoding the full-length melanoma antigen MART-1/Melan-A (MART-1).
845	18317358	This vaccine was designed to activate MART-1-specific CD+8 and CD4+ T cells.
846	18317358	CD8+ T-cell responses to MART-1 27-35 were assessed by both major histocompatibility complex class I tetramer and interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) before, during, and after each vaccine and CD4+ T-cell responses to MART-1 51-73 were followed by IFN-gamma ELISPOT.
847	18317358	Determinant spreading from the immunizing antigen MART-1 to other melanoma antigens [gp100, tyrosinase, human melanoma antigen-A3 (MAGE-A3)] was assessed by IFN-gamma ELISPOT.
848	18317358	Significant CD8+ and/or CD4+ MART-1-specific T-cell responses were observed in 6/11 and 2/4 patients evaluated, respectively, indicating that the E1-deleted adenovirus encoding the cDNA for MART-1/Melan-A (AdVMART1)/DC vaccine activated both helper and killer T cells in vivo.
849	18317358	Responses in CD8+ and CD4+ T cells to additional antigens were noted in 2 patients.
850	18317358	We performed a phase 1/2 trial testing the safety, toxicity, and immune response of a vaccine consisting of autologous dendritic cells (DCs) transduced with a replication-defective adenovirus (AdV) encoding the full-length melanoma antigen MART-1/Melan-A (MART-1).
851	18317358	This vaccine was designed to activate MART-1-specific CD+8 and CD4+ T cells.
852	18317358	CD8+ T-cell responses to MART-1 27-35 were assessed by both major histocompatibility complex class I tetramer and interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) before, during, and after each vaccine and CD4+ T-cell responses to MART-1 51-73 were followed by IFN-gamma ELISPOT.
853	18317358	Determinant spreading from the immunizing antigen MART-1 to other melanoma antigens [gp100, tyrosinase, human melanoma antigen-A3 (MAGE-A3)] was assessed by IFN-gamma ELISPOT.
854	18317358	Significant CD8+ and/or CD4+ MART-1-specific T-cell responses were observed in 6/11 and 2/4 patients evaluated, respectively, indicating that the E1-deleted adenovirus encoding the cDNA for MART-1/Melan-A (AdVMART1)/DC vaccine activated both helper and killer T cells in vivo.
855	18317358	Responses in CD8+ and CD4+ T cells to additional antigens were noted in 2 patients.
856	18317358	We performed a phase 1/2 trial testing the safety, toxicity, and immune response of a vaccine consisting of autologous dendritic cells (DCs) transduced with a replication-defective adenovirus (AdV) encoding the full-length melanoma antigen MART-1/Melan-A (MART-1).
857	18317358	This vaccine was designed to activate MART-1-specific CD+8 and CD4+ T cells.
858	18317358	CD8+ T-cell responses to MART-1 27-35 were assessed by both major histocompatibility complex class I tetramer and interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) before, during, and after each vaccine and CD4+ T-cell responses to MART-1 51-73 were followed by IFN-gamma ELISPOT.
859	18317358	Determinant spreading from the immunizing antigen MART-1 to other melanoma antigens [gp100, tyrosinase, human melanoma antigen-A3 (MAGE-A3)] was assessed by IFN-gamma ELISPOT.
860	18317358	Significant CD8+ and/or CD4+ MART-1-specific T-cell responses were observed in 6/11 and 2/4 patients evaluated, respectively, indicating that the E1-deleted adenovirus encoding the cDNA for MART-1/Melan-A (AdVMART1)/DC vaccine activated both helper and killer T cells in vivo.
861	18317358	Responses in CD8+ and CD4+ T cells to additional antigens were noted in 2 patients.
862	18481391	The plasmid encoded T-cell epitopes from differentiation antigens Melan-A/melanoma antigen recognized by T cells (MART)-1 and tyrosinase, encompassing amino acids 26-35 and 31-70 from Melan-A/MART-1, and 1-9 as well as 369-377 from tyrosinase.
863	18481391	There was a correlation between time to progression (TTP) and Melan-A/MART-1 immunity (preexisting or induced) for all patients.
864	18481391	The plasmid encoded T-cell epitopes from differentiation antigens Melan-A/melanoma antigen recognized by T cells (MART)-1 and tyrosinase, encompassing amino acids 26-35 and 31-70 from Melan-A/MART-1, and 1-9 as well as 369-377 from tyrosinase.
865	18481391	There was a correlation between time to progression (TTP) and Melan-A/MART-1 immunity (preexisting or induced) for all patients.
866	18573812	Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor.
867	18573812	Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma.
868	18573812	In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen.
869	18573812	Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma.
870	18573812	Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen.
871	18573812	Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor.
872	18573812	Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma.
873	18573812	In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen.
874	18573812	Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma.
875	18573812	Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen.
876	18573812	Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor.
877	18573812	Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma.
878	18573812	In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen.
879	18573812	Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma.
880	18573812	Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen.
881	18573812	Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor.
882	18573812	Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma.
883	18573812	In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen.
884	18573812	Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma.
885	18573812	Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen.
886	18573812	Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor.
887	18573812	Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma.
888	18573812	In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen.
889	18573812	Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma.
890	18573812	Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen.
891	18695871	Melanoma-associated antigens, MART-1, tyrosinase, gp100 and MAGEs, are typical melanoma-specific tumor antigens which can potently induce immune responses in metastatic melanoma patients treated with peptide vaccines.
892	18695871	In the present study, we established a dendritic cell (DC)-based HLA-A2 melanoma-associated peptide (MART-1 or gp100)-specific CTL induction method and characterized the CTLs using HLA-A2 tetramer staining in 6 cases of HLA-A2+ melanoma treated with DC vaccines.
893	18695871	Peripheral blood mononuclear cells (PBMC) from patients were stimulated twice with MART-1 A2 peptide-pulsed DCs in the presence of a low dose of IL-2.
894	18695871	Finally, we were successful in identifying melanoma peptide-specific T-cell receptor (TCR) cDNAs in 2 cases for MART-1 and 1 case for gp100 using the anti-TCR MoAb-based sorting as a novel approach instead of a conventional cell cloning, and confirmed peptide-specific IFN-gamma production in TCR cDNA-transduced naïve T cells.
895	18695871	Melanoma-associated antigens, MART-1, tyrosinase, gp100 and MAGEs, are typical melanoma-specific tumor antigens which can potently induce immune responses in metastatic melanoma patients treated with peptide vaccines.
896	18695871	In the present study, we established a dendritic cell (DC)-based HLA-A2 melanoma-associated peptide (MART-1 or gp100)-specific CTL induction method and characterized the CTLs using HLA-A2 tetramer staining in 6 cases of HLA-A2+ melanoma treated with DC vaccines.
897	18695871	Peripheral blood mononuclear cells (PBMC) from patients were stimulated twice with MART-1 A2 peptide-pulsed DCs in the presence of a low dose of IL-2.
898	18695871	Finally, we were successful in identifying melanoma peptide-specific T-cell receptor (TCR) cDNAs in 2 cases for MART-1 and 1 case for gp100 using the anti-TCR MoAb-based sorting as a novel approach instead of a conventional cell cloning, and confirmed peptide-specific IFN-gamma production in TCR cDNA-transduced naïve T cells.
899	18695871	Melanoma-associated antigens, MART-1, tyrosinase, gp100 and MAGEs, are typical melanoma-specific tumor antigens which can potently induce immune responses in metastatic melanoma patients treated with peptide vaccines.
900	18695871	In the present study, we established a dendritic cell (DC)-based HLA-A2 melanoma-associated peptide (MART-1 or gp100)-specific CTL induction method and characterized the CTLs using HLA-A2 tetramer staining in 6 cases of HLA-A2+ melanoma treated with DC vaccines.
901	18695871	Peripheral blood mononuclear cells (PBMC) from patients were stimulated twice with MART-1 A2 peptide-pulsed DCs in the presence of a low dose of IL-2.
902	18695871	Finally, we were successful in identifying melanoma peptide-specific T-cell receptor (TCR) cDNAs in 2 cases for MART-1 and 1 case for gp100 using the anti-TCR MoAb-based sorting as a novel approach instead of a conventional cell cloning, and confirmed peptide-specific IFN-gamma production in TCR cDNA-transduced naïve T cells.
903	18695871	Melanoma-associated antigens, MART-1, tyrosinase, gp100 and MAGEs, are typical melanoma-specific tumor antigens which can potently induce immune responses in metastatic melanoma patients treated with peptide vaccines.
904	18695871	In the present study, we established a dendritic cell (DC)-based HLA-A2 melanoma-associated peptide (MART-1 or gp100)-specific CTL induction method and characterized the CTLs using HLA-A2 tetramer staining in 6 cases of HLA-A2+ melanoma treated with DC vaccines.
905	18695871	Peripheral blood mononuclear cells (PBMC) from patients were stimulated twice with MART-1 A2 peptide-pulsed DCs in the presence of a low dose of IL-2.
906	18695871	Finally, we were successful in identifying melanoma peptide-specific T-cell receptor (TCR) cDNAs in 2 cases for MART-1 and 1 case for gp100 using the anti-TCR MoAb-based sorting as a novel approach instead of a conventional cell cloning, and confirmed peptide-specific IFN-gamma production in TCR cDNA-transduced naïve T cells.
907	18945350	Validation of a HLA-A2 tetramer flow cytometric method, IFNgamma real time RT-PCR, and IFNgamma ELISPOT for detection of immunologic response to gp100 and MelanA/MART-1 in melanoma patients.
908	18985183	The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Perillyl alcohol, Perphenazine 4-aminobutyrate, PeviPRO/breast cancer, PF-03814735, PHA-739358, Pimecrolimus, Plitidepsin, Posaconazole, Prasterone, Prasugrel, Pregabalin, Prucalopride, PRX-08066; rAAV2-TNFR:Fc, Ranelic acid distrontium salt, Ranibizumab, rCD154-CLL, Retapamulin, RTS,S/SBAS2, rV-PSA-TRICOM/rF-PSA-TRICOM; SG-2000, Sinecatechins, Sirolimus-eluting stent, Sorafenib, SP-1640, Strontium malonate, Succinobucol, Sunitinib malate; Taxus, Teduglutide, Telavancin hydrochloride, Telbivudine, Telmisartan/hydrochlorothiazide, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tocilizumab; Ustekinumab; V-5 Immunitor, Voriconazole, Vorinostat; Xience V, XL-184, XL-647, XL-765; Y-39983, Zibotentan.
909	19124729	A20 down-regulated DCs showed higher activation of the transcription factors NF-kappaB and activator protein-1, which resulted in increased and sustained production of IL-6, IL-10, and IL-12p70.
910	19124729	We further demonstrated that A20 down-regulated DCs skew naive CD4+ T cells toward IFN-gamma producing Th1 cells, a process which is dependent on IL-12p70 and which is unaffected by IL-10.
911	19124729	Furthermore, A20 and/or IL-10 down-regulated DCs had an enhanced capacity to prime Melan-A/MART-1 specific CD8+ T cells.
912	19124729	Finally, we demonstrated that potent T cell stimulatory DCs are generated by the simultaneous delivery of poly(I:C12U), A20, or A20/IL-10 small interfering RNA and Ag-encoding mRNA, introducing a one step approach to improve DC-based vaccines.
913	19124729	Together these findings demonstrate that A20 negatively regulates NF-kappaB and activator protein-1 in DCs and that down-regulation of A20 results in DCs with enhanced T cell stimulatory capacity.
914	19483648	The frequency of Melan-A analog specific CD8+ T-cells was detected by using tetramers.
915	19483648	Melan-A analog specific T-cells from HLA-A2+ healthy donors and HLA-A2+ MM patients showed a interferon-gamma secretion mediated by HM1.24(aa22-30) peptide-pulsed T2 cells and lysed the HLA-A2+ HM1.24+ U266 and XG-1 human myeloma derived cell-lines as well as the B-lymphoblastoid cell-line IM-9.
916	19483648	The frequency of Melan-A analog specific CD8+ T-cells was detected by using tetramers.
917	19483648	Melan-A analog specific T-cells from HLA-A2+ healthy donors and HLA-A2+ MM patients showed a interferon-gamma secretion mediated by HM1.24(aa22-30) peptide-pulsed T2 cells and lysed the HLA-A2+ HM1.24+ U266 and XG-1 human myeloma derived cell-lines as well as the B-lymphoblastoid cell-line IM-9.
918	19561536	As T cells themselves may serve as effective antigen-presenting cells (T antigen-presenting cells; TAPC) and may be useful in vivo as cellular vaccines, we examined whether CD8(+) T cells genetically modified to produce IL-21 could induce immune responses to tumor associated antigen peptides in healthy human leukocyte antigen-A2(+) donors.
919	19561536	We found that IL-21 modified TAPC enhanced both the proliferation and survival of MART-1 specific CD8(+) T cells, which were enriched by >8-fold over cultures with control nontransgenic TAPC.
920	19561536	MART-1-specific CTL produced interferon-gamma in response to cognate peptide antigen and killed primary tumor cells expressing MART-1 in a major histocompatibility complex restricted manner.
921	19561536	IL-21 modified TAPC similarly enhanced generation of functional CTL against melanoma antigen gp100 and the B-cell chronic lymphocytic leukemia associated RHAMM antigen.
922	19561536	Antigen-specific CTL generated using IL-21 gene-modified TAPC had a central memory phenotype characterized by CD45RA(-), CD44(high), CD27(high), CD28(high), CD62L(high), and IL-7 receptor-alpha(high), contrasting with the terminal effector phenotype of CTL generated in the absence of IL-21.
923	19561536	As T cells themselves may serve as effective antigen-presenting cells (T antigen-presenting cells; TAPC) and may be useful in vivo as cellular vaccines, we examined whether CD8(+) T cells genetically modified to produce IL-21 could induce immune responses to tumor associated antigen peptides in healthy human leukocyte antigen-A2(+) donors.
924	19561536	We found that IL-21 modified TAPC enhanced both the proliferation and survival of MART-1 specific CD8(+) T cells, which were enriched by >8-fold over cultures with control nontransgenic TAPC.
925	19561536	MART-1-specific CTL produced interferon-gamma in response to cognate peptide antigen and killed primary tumor cells expressing MART-1 in a major histocompatibility complex restricted manner.
926	19561536	IL-21 modified TAPC similarly enhanced generation of functional CTL against melanoma antigen gp100 and the B-cell chronic lymphocytic leukemia associated RHAMM antigen.
927	19561536	Antigen-specific CTL generated using IL-21 gene-modified TAPC had a central memory phenotype characterized by CD45RA(-), CD44(high), CD27(high), CD28(high), CD62L(high), and IL-7 receptor-alpha(high), contrasting with the terminal effector phenotype of CTL generated in the absence of IL-21.
928	19609242	We injected intradermally protamine-stabilized mRNAs coding for Melan-A, Tyrosinase, gp100, Mage-A1, Mage-A3, and Survivin in 21 metastatic melanoma patients.
929	19609242	Granulocyte macrophage colony-stimulating factor was applied as an adjuvant.
930	19609242	During treatment the frequency of Foxp3+/CD4+ regulatory T cells was significantly decreased upon mRNA vaccination in peripheral blood of the patients in the KLH arm, whereas myeloid suppressor cells (CD11b+HLA-DR lo monocytes) were reduced in the patients not receiving KLH.
931	19609245	Generation of human dendritic cells that simultaneously secrete IL-12 and have migratory capacity by adenoviral gene transfer of hCD40L in combination with IFN-gamma.
932	19609245	In this study, we exploit an adenoviral vector encoding human CD40 ligand (CD40L), Ad5hCD40L, to establish DCs that feature both migration potential and prolonged secretion of the key T-helper 1 cytokine interleukin-12p70 (IL-12p70).
933	19609245	Finally, DCs transduced with both Ad5hCD40L and an adenoviral vector encoding the melanoma antigen MelanA/MART-1 and treated with MC and IFN-gamma efficiently primed naive autologous CD8+ T cells into antigen-specific cytotoxic T lymphocyte.
934	19609245	This strategy to generate DCs that exert both migration capacity and prolonged IL-12p70 secretion after intracellular CD40L expression and IFN-gamma treatment has the potential to further improve current DC vaccination protocols.
935	19686694	In vivo anti-melanoma activities of the Melan-A/MART-1(101-115) T CD4+ cell peptide.
936	19752746	Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer membrane protein p40 as an adjuvant.
937	19752746	Here we investigated the novel Toll-like receptor2 ligand P40, the outer membrane protein A derived from Klebsiella pneumoniae.
938	19752746	Seventeen human leukocyte antigen-A*0201 positive stage III/IV melanoma patients were vaccinated with P40 and Melan-A/Mart-1 peptide subcutaneously in monthly intervals.
939	19752746	Melan-A/Mart-1 specific CD8 T cells were analyzed ex vivo, with positive results in 6 of 14 evaluable patients.
940	19752746	Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer membrane protein p40 as an adjuvant.
941	19752746	Here we investigated the novel Toll-like receptor2 ligand P40, the outer membrane protein A derived from Klebsiella pneumoniae.
942	19752746	Seventeen human leukocyte antigen-A*0201 positive stage III/IV melanoma patients were vaccinated with P40 and Melan-A/Mart-1 peptide subcutaneously in monthly intervals.
943	19752746	Melan-A/Mart-1 specific CD8 T cells were analyzed ex vivo, with positive results in 6 of 14 evaluable patients.
944	19752746	Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer membrane protein p40 as an adjuvant.
945	19752746	Here we investigated the novel Toll-like receptor2 ligand P40, the outer membrane protein A derived from Klebsiella pneumoniae.
946	19752746	Seventeen human leukocyte antigen-A*0201 positive stage III/IV melanoma patients were vaccinated with P40 and Melan-A/Mart-1 peptide subcutaneously in monthly intervals.
947	19752746	Melan-A/Mart-1 specific CD8 T cells were analyzed ex vivo, with positive results in 6 of 14 evaluable patients.
948	19758325	Towards this end, a cationic tat-sequence was fused with an antigenic, major histocompatibility complex (MHC) class I-binding melanoma epitope (Melan-A/Mart-1 sequence: ELAGIGILTV) and then mixed with negatively charged poly(I:C) dsRNA to form peptide/nucleic acid complexes.
949	19786555	In this study, we compared the TCR primary structures of 1489 HLA-A*0201/Melan-A(26-35)-specific CD8 T cells derived from both cohorts of patients.
950	19808957	Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts.
951	19808957	We have previously shown that vaccination of HLA-A2 metastatic melanoma patients with the analogue Melan-A(26-35(A27L)) peptide emulsified in a mineral oil induces ex vivo detectable specific CD8 T cells.
952	19808957	We report that the majority of melanoma patients carry high frequencies of naturally circulating HLA-DQ6-restricted Melan-A-specific CD4 T cells, a high proportion of which express FOXP3 and proliferate poorly in response to the cognate peptide.
953	19808957	In contrast, we found a marked shift to FOXP3-negative CD4 T cells, accompanied by robust CD4 T-cell proliferation upon in vitro stimulation with cognate peptide.
954	19808957	Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts.
955	19808957	We have previously shown that vaccination of HLA-A2 metastatic melanoma patients with the analogue Melan-A(26-35(A27L)) peptide emulsified in a mineral oil induces ex vivo detectable specific CD8 T cells.
956	19808957	We report that the majority of melanoma patients carry high frequencies of naturally circulating HLA-DQ6-restricted Melan-A-specific CD4 T cells, a high proportion of which express FOXP3 and proliferate poorly in response to the cognate peptide.
957	19808957	In contrast, we found a marked shift to FOXP3-negative CD4 T cells, accompanied by robust CD4 T-cell proliferation upon in vitro stimulation with cognate peptide.
958	19935776	We used a rVV encoding gp100(280-288), Melan-A/MART-1(27-35) and tyrosinase(1-9) HLA-A0201 restricted epitopes and CD80 and CD86 costimulatory molecules in stage III and IV melanoma patients in a phase 1/2 trial.
959	19935776	Of 15 patients initiating treatment, including two cycles of IN immunization, each comprising one rVV administration and three recall injections of the corresponding peptides, accompanied by subcutaneous granulocyte macrophage-colony stimulating factor supplementation, five withdrew due to progressing disease.
960	20200354	Here, we present a strategy based on the combination of tetramer staining, magnetic-bead enrichment, and multiparametric cytometry, which permitted direct detection and analysis of CD8(+) T cells reactive for 6 different naive epitopes (MART-1(26-35), HIV-1 Gag p17(77-85), hepatitis C virus [HCV] NS3(1406-1415), HCV Core(132-140), NY-ESO-1(157-165), and cytomegalovirus [CMV] pp65(495-503)).
961	20370546	Patients bearing metastatic melanoma were successfully treated with ACT using peripheral blood lymphocytes transduced with Mart-1 and gp100 tumor-associated epitopes.
962	20430956	Processing and cross-presentation of individual HLA-A, -B, or -C epitopes from NY-ESO-1 or an HLA-A epitope for Melan-A differ according to the mode of antigen delivery.
963	20430956	We studied cross-presentation of the cancer/testis antigen, NY-ESO-1, and the melanoma differentiation antigen, Melan-A by human DC subsets.
964	20430956	HLA-A2 epitope generation required endosomal acidification and was proteasome-independent for NY-ESO-1 and proteasome-dependent for Melan-A.
965	20430956	Both MoDCs and CD1c(+) blood DCs cross-presented NY-ESO-1-specific HLA-A2(157-165)-, HLA-B7(60-72)-, and HLA-Cw3(92-100)-restricted epitopes when formulated as an NY-ESO-1/ISCOMATRIX vaccine, but this was limited when NY-ESO-1 and ISCOMATRIX adjuvant were added separately to the DC cultures.
966	20430956	Processing and cross-presentation of individual HLA-A, -B, or -C epitopes from NY-ESO-1 or an HLA-A epitope for Melan-A differ according to the mode of antigen delivery.
967	20430956	We studied cross-presentation of the cancer/testis antigen, NY-ESO-1, and the melanoma differentiation antigen, Melan-A by human DC subsets.
968	20430956	HLA-A2 epitope generation required endosomal acidification and was proteasome-independent for NY-ESO-1 and proteasome-dependent for Melan-A.
969	20430956	Both MoDCs and CD1c(+) blood DCs cross-presented NY-ESO-1-specific HLA-A2(157-165)-, HLA-B7(60-72)-, and HLA-Cw3(92-100)-restricted epitopes when formulated as an NY-ESO-1/ISCOMATRIX vaccine, but this was limited when NY-ESO-1 and ISCOMATRIX adjuvant were added separately to the DC cultures.
970	20430956	Processing and cross-presentation of individual HLA-A, -B, or -C epitopes from NY-ESO-1 or an HLA-A epitope for Melan-A differ according to the mode of antigen delivery.
971	20430956	We studied cross-presentation of the cancer/testis antigen, NY-ESO-1, and the melanoma differentiation antigen, Melan-A by human DC subsets.
972	20430956	HLA-A2 epitope generation required endosomal acidification and was proteasome-independent for NY-ESO-1 and proteasome-dependent for Melan-A.
973	20430956	Both MoDCs and CD1c(+) blood DCs cross-presented NY-ESO-1-specific HLA-A2(157-165)-, HLA-B7(60-72)-, and HLA-Cw3(92-100)-restricted epitopes when formulated as an NY-ESO-1/ISCOMATRIX vaccine, but this was limited when NY-ESO-1 and ISCOMATRIX adjuvant were added separately to the DC cultures.
974	20648001	Moreover, only DCs treated with SOCS-1 siRNA, and not controls, elicited strong primary in vitro responses to well-characterized HLA-A*0201-restricted Melan-A/MART-1 and human immunodeficiency virus (HIV) Gag epitopes in naive CD8(+) T cells from healthy donors.
975	20648001	Finally, stimulation of CD8(+) T cells from HIV-seropositive subjects with SOCS1-silenced DCs resulted in an augmented polyfunctional cytotoxic T-lymphocyte (CTL) response, suggesting that SOCS-1 silencing can restore functionally compromised T cells in HIV infection.
976	20664354	As compared with CD4 T cells, CD8 T cells showed higher susceptibility to chemotherapy, followed by more rapid homeostatic proliferation and recovery, resulting in strong inversions of CD4/CD8 ratios.
977	20664354	Despite efficient homeostatic proliferation of total CD4 and CD8 T cells, the frequency of CD8 T cells specific for Melan-A and cancer-testis antigens remained relatively low.
978	20664359	In an attempt to improve persistence of the transferred lymphocytes, we cotransduced human peripheral blood lymphocytes with retroviruses encoding Bcl-2 or Bcl-xL, antiapoptotic genes of the BCL2 family, and the MART-1 melanoma tumor antigen-specific TCR, DMF5.
979	20664359	Cotransduction with Bcl-2 or Bcl-xL did not affect cytokine secretion or lytic ability of the DMF5-transduced lymphocytes.
980	20664359	Thus, by coexpressing Bcl-2 or Bcl-xL with a tumor-specific TCR, we have engineered a lymphocyte that resists apoptosis owing to IL-2 withdrawal without altering its tumor-specific function or phenotype, and thus may show improved antitumor effectiveness in vivo after cell transfer.
981	20665204	Some of these vaccines target differentiation antigens that are expressed by tumors derived from one particular tissue (e. g., Melan-A/ MART-1, tyrosinase, gp 100).
982	20665204	Some target antigens are specifically expressed in tumors of different types but not in normal tissues (e. g., MAGE-3), while other possible targets are antigens that are expressed at low level in normal tissues and are over-expressed in tumors of different types (e. g., HER2, Muc 1).
983	20725097	In addition, the T-cell response primed through this dual-antigen-expressing plasmid (MART-1/Melan-A and tyrosinase) translated into a substantial proliferation capacity and functional conversion to antitumor effector cells after tyrosinase and MART-1/Melan-A peptide analog boost.
984	20806940	Crystal structures of HLA-A*0201 complexed with Melan-A/MART-1(26(27L)-35) peptidomimetics reveal conformational heterogeneity and highlight degeneracy of T cell recognition.
985	20806940	Here, we demonstrate that antigenic peptidomimetics of the Melan-A/MART-1(26(27L)-35) melanoma antigen adopt strikingly different conformations when bound to MHC-I, highlighting the degeneracy of T cell recognition and revealing the challenges associated with mimicking native peptide conformation.
986	20806940	Crystal structures of HLA-A*0201 complexed with Melan-A/MART-1(26(27L)-35) peptidomimetics reveal conformational heterogeneity and highlight degeneracy of T cell recognition.
987	20806940	Here, we demonstrate that antigenic peptidomimetics of the Melan-A/MART-1(26(27L)-35) melanoma antigen adopt strikingly different conformations when bound to MHC-I, highlighting the degeneracy of T cell recognition and revealing the challenges associated with mimicking native peptide conformation.
988	20842051	Specifically, we linked the melanoma-specific Melan-A/Mart-1 peptide to virus-like nanoparticles loaded with A-type CpG, a ligand for toll-like receptor 9.
989	20842062	These studies demonstrated that the vaccine was able to induce HLA-A*0201-restricted T-cell responses against gp100 and NY-ESO-1, detectable directly ex vivo, in HLA-A2/K-transgenic mice.
990	20842062	The in vitro antigen presentation studies, in the absence of appropriate animal models, demonstrated that target cells infected with the vaccine construct were lysed by MAGE-1, MAGE-3 or MART-1 peptide-specific T cells.
991	20844609	Vaccine vectors based on heavily attenuated murine coronavirus genomes were generated to express epitopes from the lymphocytic choriomeningitis virus glycoprotein, or human Melan-A, in combination with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF).
992	20844609	Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8(+) T cells.
993	20844609	Vaccine vectors based on heavily attenuated murine coronavirus genomes were generated to express epitopes from the lymphocytic choriomeningitis virus glycoprotein, or human Melan-A, in combination with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF).
994	20844609	Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8(+) T cells.
995	21221122	Antigen-coupled VLPs and murine ovalbumin-specific and human melanoma-associated antigen recognized by T cells (MART-1)-specific CD8(+) T cells were used to demonstrate cross-presentation via this alternate, receptor recycling pathway, which operated independently of the proteasome and the transporter-associated with antigen presentation.
996	21307889	Across the trial population, vaccination resulted in an expansion of effector responses to both antigens, to the human leukocyte antigen A2-restricted modified epitope, melan A ELAGIGILTV, and to a panel of MHC class I- and II-restricted epitopes.
997	21400024	Here, we use three target epitopes, two derived from tumor antigens [Mart1(26-34) (M26) and Cyp1B1(239-247) (Cyp239)] and one derived from the influenza A viral antigen [FluM1(58-66) (FluM58)], to demonstrate that CD40-activated B cells, like dendritic cells, have a limited capability to process certain tumor antigens.
998	21555851	In peripheral blood from patients vaccinated with CpG and the melanoma antigen Melan-A/MART-1 peptide, we found functional effector T cell populations, with only small but nevertheless significant differences in T cells specific for persistent herpesviruses (EBV and CMV).
999	21796616	However, synthetic T-cell vaccines composed of Melan-A/MART-1 peptide, CpG and IFA can induce high frequencies of tumor-specific CD8 T-cells in PBMC of melanoma patients.
1000	21796616	The production of multiple cytokines (IFNγ, TNFα, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells.
1001	21796616	Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways.
1002	21796616	However, synthetic T-cell vaccines composed of Melan-A/MART-1 peptide, CpG and IFA can induce high frequencies of tumor-specific CD8 T-cells in PBMC of melanoma patients.
1003	21796616	The production of multiple cytokines (IFNγ, TNFα, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells.
1004	21796616	Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways.
1005	21874304	Here, employing the CD34(+)/CD14(+) AML-derived human DC progenitor cell line MUTZ3, we show that cytostatic anthraquinone-derivatives (i.e., the anthracenedione mitoxantrone and the related anthracyclin doxorubicin) induce rapid differentiation of CD34(+) DC precursors into functional antigen-presenting cells (APC) in a three-day protocol.
1006	21874304	The drugs were found to act specifically on CD34(+), and not on CD14(+) DC precursors.
1007	21874304	Importantly, these observations were confirmed for primary CD34(+) and CD14(+) DC precursors from peripheral blood.
1008	21874304	Mitoxantrone-generated DC were fully differentiated within three days and after an additional 24 h of maturation, were as capable as standard 9-day differentiated and matured DC to migrate toward the lymph node-homing chemokines CCL19 and CCL21, to induce primary allogeneic T cell proliferation, and to prime functional MART1-specific CD8(+) T lymphocytes.
1009	21937447	Here we investigated the MART-1(27-35) tumor antigen, for which anchor modification (replacement of the position two alanine with leucine) dramatically reduces or ablates antigenicity with a wide range of T cell clones despite significantly improving peptide binding to MHC.
1010	21937447	We found that anchor modification in the MART-1(27-35) antigen enhances the flexibility of both the peptide and the HLA-A*0201 molecule.
1011	21937447	Here we investigated the MART-1(27-35) tumor antigen, for which anchor modification (replacement of the position two alanine with leucine) dramatically reduces or ablates antigenicity with a wide range of T cell clones despite significantly improving peptide binding to MHC.
1012	21937447	We found that anchor modification in the MART-1(27-35) antigen enhances the flexibility of both the peptide and the HLA-A*0201 molecule.
1013	21940815	It has been observed that LAM cells express markers associated with melanocytic differentiation, including gp100 and MART-1.
1014	21993558	MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
1015	21993558	MART-1 and gp100 are prototypical melanoma antigen (Ag), but their clinical use as vaccines or as targets of cytotoxic lymphocytes achieved modest success.
1016	21993558	Possible explanations could be that as MART-1 and gp100 are melanocyte differentiation Ag, clonogenic Ag-non-expressing cells would be spared by immune effectors, or that clonogenic cells would be intrinsically resistant to cytotoxic lymphocytes.
1017	21993558	We therefore analyzed the proliferative status of MART-1/gp100-expressing and -non-expressing cells in biopsies, and the clonogenicity and sensitiveness to cytotoxic lymphocytes of the human cutaneous melanoma cell lines MEL-XY1 and MEL-XY3.
1018	21993558	Analysis of MART-1/gp100 and Ki-67 expression in 22 melanoma tumors revealed that MART-1/gp100-expressing and -non-expressing cells proliferated competitively.
1019	21993558	MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
1020	21993558	Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
1021	21993558	Thus, MART-1 and gp100 expression and plasticity would not interfere with proliferation or clonogenicity, and clonogenic cells may be lysed by cytotoxic lymphocytes.
1022	21993558	MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
1023	21993558	MART-1 and gp100 are prototypical melanoma antigen (Ag), but their clinical use as vaccines or as targets of cytotoxic lymphocytes achieved modest success.
1024	21993558	Possible explanations could be that as MART-1 and gp100 are melanocyte differentiation Ag, clonogenic Ag-non-expressing cells would be spared by immune effectors, or that clonogenic cells would be intrinsically resistant to cytotoxic lymphocytes.
1025	21993558	We therefore analyzed the proliferative status of MART-1/gp100-expressing and -non-expressing cells in biopsies, and the clonogenicity and sensitiveness to cytotoxic lymphocytes of the human cutaneous melanoma cell lines MEL-XY1 and MEL-XY3.
1026	21993558	Analysis of MART-1/gp100 and Ki-67 expression in 22 melanoma tumors revealed that MART-1/gp100-expressing and -non-expressing cells proliferated competitively.
1027	21993558	MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
1028	21993558	Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
1029	21993558	Thus, MART-1 and gp100 expression and plasticity would not interfere with proliferation or clonogenicity, and clonogenic cells may be lysed by cytotoxic lymphocytes.
1030	21993558	MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
1031	21993558	MART-1 and gp100 are prototypical melanoma antigen (Ag), but their clinical use as vaccines or as targets of cytotoxic lymphocytes achieved modest success.
1032	21993558	Possible explanations could be that as MART-1 and gp100 are melanocyte differentiation Ag, clonogenic Ag-non-expressing cells would be spared by immune effectors, or that clonogenic cells would be intrinsically resistant to cytotoxic lymphocytes.
1033	21993558	We therefore analyzed the proliferative status of MART-1/gp100-expressing and -non-expressing cells in biopsies, and the clonogenicity and sensitiveness to cytotoxic lymphocytes of the human cutaneous melanoma cell lines MEL-XY1 and MEL-XY3.
1034	21993558	Analysis of MART-1/gp100 and Ki-67 expression in 22 melanoma tumors revealed that MART-1/gp100-expressing and -non-expressing cells proliferated competitively.
1035	21993558	MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
1036	21993558	Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
1037	21993558	Thus, MART-1 and gp100 expression and plasticity would not interfere with proliferation or clonogenicity, and clonogenic cells may be lysed by cytotoxic lymphocytes.
1038	21993558	MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
1039	21993558	MART-1 and gp100 are prototypical melanoma antigen (Ag), but their clinical use as vaccines or as targets of cytotoxic lymphocytes achieved modest success.
1040	21993558	Possible explanations could be that as MART-1 and gp100 are melanocyte differentiation Ag, clonogenic Ag-non-expressing cells would be spared by immune effectors, or that clonogenic cells would be intrinsically resistant to cytotoxic lymphocytes.
1041	21993558	We therefore analyzed the proliferative status of MART-1/gp100-expressing and -non-expressing cells in biopsies, and the clonogenicity and sensitiveness to cytotoxic lymphocytes of the human cutaneous melanoma cell lines MEL-XY1 and MEL-XY3.
1042	21993558	Analysis of MART-1/gp100 and Ki-67 expression in 22 melanoma tumors revealed that MART-1/gp100-expressing and -non-expressing cells proliferated competitively.
1043	21993558	MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
1044	21993558	Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
1045	21993558	Thus, MART-1 and gp100 expression and plasticity would not interfere with proliferation or clonogenicity, and clonogenic cells may be lysed by cytotoxic lymphocytes.
1046	21993558	MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
1047	21993558	MART-1 and gp100 are prototypical melanoma antigen (Ag), but their clinical use as vaccines or as targets of cytotoxic lymphocytes achieved modest success.
1048	21993558	Possible explanations could be that as MART-1 and gp100 are melanocyte differentiation Ag, clonogenic Ag-non-expressing cells would be spared by immune effectors, or that clonogenic cells would be intrinsically resistant to cytotoxic lymphocytes.
1049	21993558	We therefore analyzed the proliferative status of MART-1/gp100-expressing and -non-expressing cells in biopsies, and the clonogenicity and sensitiveness to cytotoxic lymphocytes of the human cutaneous melanoma cell lines MEL-XY1 and MEL-XY3.
1050	21993558	Analysis of MART-1/gp100 and Ki-67 expression in 22 melanoma tumors revealed that MART-1/gp100-expressing and -non-expressing cells proliferated competitively.
1051	21993558	MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
1052	21993558	Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
1053	21993558	Thus, MART-1 and gp100 expression and plasticity would not interfere with proliferation or clonogenicity, and clonogenic cells may be lysed by cytotoxic lymphocytes.
1054	21993558	MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
1055	21993558	MART-1 and gp100 are prototypical melanoma antigen (Ag), but their clinical use as vaccines or as targets of cytotoxic lymphocytes achieved modest success.
1056	21993558	Possible explanations could be that as MART-1 and gp100 are melanocyte differentiation Ag, clonogenic Ag-non-expressing cells would be spared by immune effectors, or that clonogenic cells would be intrinsically resistant to cytotoxic lymphocytes.
1057	21993558	We therefore analyzed the proliferative status of MART-1/gp100-expressing and -non-expressing cells in biopsies, and the clonogenicity and sensitiveness to cytotoxic lymphocytes of the human cutaneous melanoma cell lines MEL-XY1 and MEL-XY3.
1058	21993558	Analysis of MART-1/gp100 and Ki-67 expression in 22 melanoma tumors revealed that MART-1/gp100-expressing and -non-expressing cells proliferated competitively.
1059	21993558	MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
1060	21993558	Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
1061	21993558	Thus, MART-1 and gp100 expression and plasticity would not interfere with proliferation or clonogenicity, and clonogenic cells may be lysed by cytotoxic lymphocytes.
1062	21993558	MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
1063	21993558	MART-1 and gp100 are prototypical melanoma antigen (Ag), but their clinical use as vaccines or as targets of cytotoxic lymphocytes achieved modest success.
1064	21993558	Possible explanations could be that as MART-1 and gp100 are melanocyte differentiation Ag, clonogenic Ag-non-expressing cells would be spared by immune effectors, or that clonogenic cells would be intrinsically resistant to cytotoxic lymphocytes.
1065	21993558	We therefore analyzed the proliferative status of MART-1/gp100-expressing and -non-expressing cells in biopsies, and the clonogenicity and sensitiveness to cytotoxic lymphocytes of the human cutaneous melanoma cell lines MEL-XY1 and MEL-XY3.
1066	21993558	Analysis of MART-1/gp100 and Ki-67 expression in 22 melanoma tumors revealed that MART-1/gp100-expressing and -non-expressing cells proliferated competitively.
1067	21993558	MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
1068	21993558	Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
1069	21993558	Thus, MART-1 and gp100 expression and plasticity would not interfere with proliferation or clonogenicity, and clonogenic cells may be lysed by cytotoxic lymphocytes.
1070	21993558	MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
1071	21993558	MART-1 and gp100 are prototypical melanoma antigen (Ag), but their clinical use as vaccines or as targets of cytotoxic lymphocytes achieved modest success.
1072	21993558	Possible explanations could be that as MART-1 and gp100 are melanocyte differentiation Ag, clonogenic Ag-non-expressing cells would be spared by immune effectors, or that clonogenic cells would be intrinsically resistant to cytotoxic lymphocytes.
1073	21993558	We therefore analyzed the proliferative status of MART-1/gp100-expressing and -non-expressing cells in biopsies, and the clonogenicity and sensitiveness to cytotoxic lymphocytes of the human cutaneous melanoma cell lines MEL-XY1 and MEL-XY3.
1074	21993558	Analysis of MART-1/gp100 and Ki-67 expression in 22 melanoma tumors revealed that MART-1/gp100-expressing and -non-expressing cells proliferated competitively.
1075	21993558	MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
1076	21993558	Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
1077	21993558	Thus, MART-1 and gp100 expression and plasticity would not interfere with proliferation or clonogenicity, and clonogenic cells may be lysed by cytotoxic lymphocytes.
1078	22021080	ECOG 1696 was a Phase II multi-center trial testing vaccination with melanoma peptides, gp100, MART-1 and tyrosinase delivered alone, with GM-CSF, IFN-α2b or both cytokines to HLA-A2(+) patients with metastatic melanoma.
1079	22021080	Multiparameter flow cytometry was used to measure the frequency of CD8(+) T cells specific for gp100, MART-1, tyrosinase and influenza (FLU) peptides.
1080	22021080	Expression of CD45RA/CCR7 on CD8(+) tet(+) T cells and CD25, CD27, CD28 on all circulating T cells was determined.
1081	22021080	Only gp100- and MART-1-specific T cells differentiated to CD45RA(+) CCR7(-) effector/memory T cells.
1082	22021080	Delivery of GM-CSF and/or IFN-α2b had no effects on the frequency or differentiation of CD8(+) tet(+) , CD8+ or CD4+ T cells.
1083	22021080	ECOG 1696 was a Phase II multi-center trial testing vaccination with melanoma peptides, gp100, MART-1 and tyrosinase delivered alone, with GM-CSF, IFN-α2b or both cytokines to HLA-A2(+) patients with metastatic melanoma.
1084	22021080	Multiparameter flow cytometry was used to measure the frequency of CD8(+) T cells specific for gp100, MART-1, tyrosinase and influenza (FLU) peptides.
1085	22021080	Expression of CD45RA/CCR7 on CD8(+) tet(+) T cells and CD25, CD27, CD28 on all circulating T cells was determined.
1086	22021080	Only gp100- and MART-1-specific T cells differentiated to CD45RA(+) CCR7(-) effector/memory T cells.
1087	22021080	Delivery of GM-CSF and/or IFN-α2b had no effects on the frequency or differentiation of CD8(+) tet(+) , CD8+ or CD4+ T cells.
1088	22021080	ECOG 1696 was a Phase II multi-center trial testing vaccination with melanoma peptides, gp100, MART-1 and tyrosinase delivered alone, with GM-CSF, IFN-α2b or both cytokines to HLA-A2(+) patients with metastatic melanoma.
1089	22021080	Multiparameter flow cytometry was used to measure the frequency of CD8(+) T cells specific for gp100, MART-1, tyrosinase and influenza (FLU) peptides.
1090	22021080	Expression of CD45RA/CCR7 on CD8(+) tet(+) T cells and CD25, CD27, CD28 on all circulating T cells was determined.
1091	22021080	Only gp100- and MART-1-specific T cells differentiated to CD45RA(+) CCR7(-) effector/memory T cells.
1092	22021080	Delivery of GM-CSF and/or IFN-α2b had no effects on the frequency or differentiation of CD8(+) tet(+) , CD8+ or CD4+ T cells.
1093	22057679	Here, we analysed human CD4(+) T-cell responses to vaccination with MelQbG10, which is a Qβ-VLP covalently linked to a long peptide derived from the melanoma self-antigen Melan-A.
1094	22057679	Although less strong, comparable B- and CD4(+) T-cell responses were also found specific for the Melan-A cargo peptide.
1095	22057679	Here, we analysed human CD4(+) T-cell responses to vaccination with MelQbG10, which is a Qβ-VLP covalently linked to a long peptide derived from the melanoma self-antigen Melan-A.
1096	22057679	Although less strong, comparable B- and CD4(+) T-cell responses were also found specific for the Melan-A cargo peptide.
1097	22080404	To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund's adjuvant.
1098	22080404	Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups.
1099	22080404	Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo.
1100	22080404	In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers.
1101	22080404	To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund's adjuvant.
1102	22080404	Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups.
1103	22080404	Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo.
1104	22080404	In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers.
1105	22080404	To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund's adjuvant.
1106	22080404	Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups.
1107	22080404	Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo.
1108	22080404	In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers.
1109	22080404	To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund's adjuvant.
1110	22080404	Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups.
1111	22080404	Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo.
1112	22080404	In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers.
1113	22116674	Herpes simplex virus protein ICP47, encoded by US12 gene, strongly downregulates major histocompatibility complex (MHC) class-I antigen restricted presentation by blocking transporter associated with antigen processing (TAP) protein.
1114	22116674	To decrease viral vector antigenic immunodominance and MHC class-I driven clearance, we engineered recombinant vaccinia viruses (rVV) expressing ICP47 alone (rVV-US12) or together with endoplasmic reticulum (ER)-targeted Melan-A/MART-1(27-35) model tumor epitope (rVV-MUS12).
1115	22116674	In this study, we show that antigen presenting cells (APC), infected with rVV-US12, display a decreased ability to present TAP dependent MHC class-I restricted viral antigens to CD8+ T-cells.
1116	22116674	While HLA class-I cell surface expression is strongly downregulated, other important immune related molecules such as CD80, CD44 and, most importantly, MHC class-II are unaffected.
1117	22130166	Increased antibody levels were also observed to the tumor antigens Melan-A, MAGE-A4, SSX2, and p53.
1118	22130166	For peripheral T-cell populations, statistically significant increases in the percent of activated (HLA-DR) CD4 and CD8 T cells with concomitant decreases in naive CD4 and CD8 T cells were observed after ipilimumab treatment.
1119	22130166	Increases were also observed in central memory, effector memory, and activated ICOS CD4 T cells, but not in ICOS CD8 T cells or in FoxP3 CD4 regulatory T cells.
1120	22495394	Safety and immunogenicity of vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) in adjuvant with PF-3512676 and GM-CSF in metastatic melanoma.
1121	22495394	Our objective was to determine the safety and immunogenicity of vaccination against melanoma-related antigens employing MART-1, gp100, and tysosinase paptides combined with the TLR9 agonist PF-3512676 and local granulocyte macrophage-colony stimulating factor in oil emulsion.
1122	22495394	Our adjuvant regimen combining PF-3512676 and granulocyte macrophage-colony stimulating factor was safe and is worthy of further testing with these or alternative peptides, potentially in combination with antibodies that target immunoregulatory checkpoints.
1123	22495394	Safety and immunogenicity of vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) in adjuvant with PF-3512676 and GM-CSF in metastatic melanoma.
1124	22495394	Our objective was to determine the safety and immunogenicity of vaccination against melanoma-related antigens employing MART-1, gp100, and tysosinase paptides combined with the TLR9 agonist PF-3512676 and local granulocyte macrophage-colony stimulating factor in oil emulsion.
1125	22495394	Our adjuvant regimen combining PF-3512676 and granulocyte macrophage-colony stimulating factor was safe and is worthy of further testing with these or alternative peptides, potentially in combination with antibodies that target immunoregulatory checkpoints.
1126	22722447	Lipid bodies do not contain the melanoma-associated antigen MART-1.
1127	22722447	However, when a maturation cocktail composed of TNF-alpha, IL-6, IL-1beta and prostaglandin E2 is added to the coculture, the tumor cells clumps disaggregate, dendritic cells remain free in suspension and their ability to efficiently stimulate allogeneic lymphocytes is restored.
1128	22735807	We have previously shown that vaccination with the natural tumor peptide Melan-A-induced T cells with superior effector functions as compared with vaccination with the analog peptide optimized for enhanced HLA-A*0201 binding.
1129	22735807	Here we found that natural peptide vaccination induced tumor-reactive CD8 T cells with frequent coexpression of both memory/homing-associated genes (CD27, IL7R, EOMES, CXCR3, and CCR5) and effector-related genes (IFNG, KLRD1, PRF1, and GZMB), comparable with protective Epstein-Barr virus-specific and cytomegalovirus-specific T cells.
1130	22895835	Briefly, a cocktail of 5 melanoma-associated synthetic peptides (gp100, tyrosinase, MAGE-A2, MAGE-A3 and MART-1 or MAGE‑A1) restricted to HLA-A2 or A24 and KLH were used for DC pulsing.
1131	22895835	Based on immunohistochemical analysis, CD8 and IL-17 were not involved in the prognosis.
1132	22970293	In this study, we have identified a novel HLA-B*1801-restricted CD8(+) T cell epitope, NY-ESO-1(88-96) (LEFYLAMPF) and compared its direct- and cross-presentation to that of the reported NY-ESO-1(157-165) epitope restricted to HLA-A*0201.
1133	22970293	On the other hand, NY-ESO-1(157-165) is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A(26-35); whereas NY-ESO-1(88-96) was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome.
1134	23090079	Differing patterns of circulating regulatory T cells and myeloid-derived suppressor cells in metastatic melanoma patients receiving anti-CTLA4 antibody and interferon-α or TLR-9 agonist and GM-CSF with peptide vaccination.
1135	23090079	The second [toll-like receptor 9 (TLR)/GM] tested vaccination with MART-1, gp100, tyrosinase given with TLR-9 agonist and granulocyte-macrophage colony-stimulating factor and reported 9% response rate, median progression-free survival of 1.9 months, and median overall survival of 13.4 months.
1136	23090079	The CD4(+)CD25hi(+)CD39(+) T-reg percentage was increased most at day 85 (P = 0.018) and less significantly at day 29 (P = 0.09).
1137	23090079	T-reg findings suggest that IFN/treme induced clinically significant antitumor responses by inhibiting CTLA4 suppressive effects on T effectors, and less so by affecting T-reg.
1138	23108144	In parallel experiments, using NOD/SCID/IL-2rγc(null)-immunodeficient (hDC-NOG) mouse model, we also showed that the human melanoma antigen, MART-1, expressed by mRNA transfected aAVCs can be cross-presented to antigen-specific T cells by human dendritic cells.
1139	23200882	Monocyte-derived dendritic cells (DCs) used for immunotherapy e.g. against cancer are commonly matured by pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and prostaglandin E(2) although the absence of Toll-like receptor mediated activation prevents secretion of IL-12 from DCs and subsequent efficient induction of type 1 effector T cells.
1140	23200882	Standard matured clinical grade DCs "sDCs" were compared with DCs matured with either of two type 1 polarizing maturation cocktails; the alpha-type-1 DCs "αDC1s" (TNF-α, IL-1β, IFN-γ, IFN-α, Poly(I:C)) and "mDCs" (monophosphoryl lipid A (MPL), IFN-γ) or a mixed cocktail - "mpDCs", containing MPL, IFN-γ and PGE(2). αDC1s and mDCs secreted IL-12 directly and following re-stimulation with CD40L-expressing cells and they mainly secreted the T effector cell attracting chemokines CXCL10 and CCL5 as opposed to sDCs that mainly secreted CCL22, known to attract regulatory T cells. αDC1s and mDCs were functionally superior to sDCs as they polarized naïve CD4(+) T cells most efficiently into T helper type 1 effector cells and primed more functional MART-1 specific CD8(+) T cells although with variation between donors. αDC1s and mDCs were transiently less capable of CCL21-directed transwell migration than standard matured DCs, likely due to their increased secretion of CCL19, which mediate internalization of CCR7. mpDCs were intermediate between standard and polarized DCs both in terms of IL-12 secretion and transwell migratory ability but functionally they resembled sDCs and strikingly had the highest expression of the inhibitory molecules PD-L1 and CD25.
1141	23811433	We found that lentivirus-mediated transduction of cMYC along with BMI1 induced proliferation of CD14(+) monocytes derived from 9 out of 12 blood donors, and we named the monocyte-derived proliferating cells CD14-ML.
1142	23811433	Their proliferation continued for 3-5 weeks in the presence of M-CSF and GM-CSF, resulting in 20-1000-fold amplification.
1143	23811433	We successfully stimulated autologous CD8(+) T cells with CD14-ML-DC pulsed with cytomegalovirus peptide or MART-1 peptide to generate antigen-specific CTL lines.
1144	23833682	These cells express differential amounts of various melanoma associated antigens such as MART-1, gp100 (Pmel17), MAGE-A1 and tyrosinase as well a cell surface antigens essential for melanoma cell metastasis, such as CD146 and CD71.
1145	24316552	Mature DCs (mDCs) induced by the combination of v-FlaB/TNFα/IFNα were significantly more potent in inducing specific anticancer immune responses compared with the standard DCs that were maturated by the conventional cytokine cocktail of TNFα/IL-1β/IL-6/PGE(2).
1146	24316552	The potent mDCs produced a higher level of interleukin (IL)-12p70 and polarized naive CD4(+) T cells more towards Th1-type cells, markedly increased antigen-specific CD8(+) T-cell number and significantly enhanced the induction of lytic enzymes in antigen-specific CD8(+) CTLs and sensitized CD3(+) T cells to produce higher number of interferon (IFN)γ-secreting cells.
1147	24316552	As a result, the mDCs produced more potent antigen-specific CTLs against the MART-1 and expressed higher levels of homing receptors CCR5 and CXCR3.
1148	24713579	Artificial antigen-presenting cells expressing CD80, CD70, and 4-1BB ligand efficiently expand functional T cells specific to tumor-associated antigens.
1149	24713579	Here, in order to develop a novel aAPC system, we established K562 erythroleukemia cells expressing different combinations of co-stimulatory molecule ligands, CD80, CD70, and/or 4-1BB ligand (4-1BBL).
1150	24713579	When nucleofected with in vitro-generated mRNA encoding a tumor-associated antigen, MART-1, the K562 cells expressing all of CD80, CD70, and 4-1BBL were the most efficient for expansion of functional T cells specific to an HLA-A2-restricted immunodominant epitope, MART-126-35.
1151	24713579	In addition, only the K562 cells expressing all three of these co-stimulatory molecule ligands could clearly expand T cells specific to other less immunogenic antigen epitopes, gp100154-162 and Cyp1B1239-247, through transfection with in vitro generated gp100 and Cyp1B1 mRNA, respectively.
1152	24713579	These results indicated that non-redundant and synergistic effects of co-stimulation via CD28/CD80, CD27/CD70, and 4-1BB/4-1BBL might be critical for eliciting efficient expansion of T cells; co-stimulation via the 4-1BB/4-1BBL interaction might expand antigen-specific T cells by preventing apoptotic cell death triggered by specific antigens in the presence of the CD28/CD80 and CD27/CD70 signaling.
1153	24713579	Taken together, our findings suggested that this K562-based aAPC system expressing CD80, CD70, and 4-1BBL would be useful for efficiently stimulating functional antigen-specific T cells ex vivo, in particular when detailed information on the epitope specificities is unavailable.
1154	24756419	The 6MHP vaccine is comprised of 6 peptides representing melanocytic differentiation proteins gp100, tyrosinase, Melan-A/MART-1, and cancer testis antigens from the MAGE family.
1155	24756419	CD4(+) and CD8(+) T cell responses were assessed in peripheral blood and in sentinel immunized nodes (SIN) by thymidine uptake after exposure to helper peptides and by direct interferon-γ ELIspot assay against 14 MHC class I-restricted peptides.
1156	24756419	The 6MHP vaccine induces both CD4(+) and CD8(+) T cell responses against melanoma antigens.
1157	24825342	Topical rather than intradermal application of the TLR7 ligand imiquimod leads to human dermal dendritic cell maturation and CD8+ T-cell cross-priming.
1158	24825342	Moreover, Aldara-treated DCs showed highest levels of the costimulatory molecules CD86, CD83, CD40, and CD70.
1159	24825342	When combined with intradermal peptide vaccination, Aldara-stimulated DCs showed enhanced cross-presentation of the melanoma antigen MART-1, which resulted in increased priming and activation of MART-1-specific CD8(+) T cells.
1160	25471691	The best-studied system to date is the decamer MART-1/Melan-A26-35 peptide, EAAGIGILTV, where the natural alanine at position 2 has been modified to leucine to improve human leukocyte antigen (HLA)-A*0201 anchoring.
1161	25581444	The Melan-A/MART-126-35 peptide epitope is an example where T cells can make this distinction, with the natural peptide stimulating higher affinity CD8(+) T cells than the heteroclitic peptide, despite the heteroclitic peptide's more stable association with HLA-A2.
1162	25610730	Injection of either fluorescently-labelled ACRs or blebs alone did not affect the number or distribution of migrated DC subsets from skin biopsies after 48 hours, but resulted in a general up-regulation of the co-stimulatory molecules CD83 and CD86 on skin DCs that had ingested apoptotic material.
1163	25610730	We have previously shown that i.d. administration of GM-CSF and IL-4 resulted in preferential migration of a mature and highly T cell-stimulatory CD11hiCD1a+CD14- dermal DC subset.
1164	25610730	Here, we found that co-injection of GM-CSF and IL-4 together with either ACRs or blebs resulted in uptake efficiencies within this dermal DC subset of 7.6% (±6.1%) and 19.1% (±15.9%), respectively, thus revealing a significantly higher uptake frequency of blebs (P < 0.02).
1165	25610730	Nevertheless, in contrast to i.d. administration of ACR, the injection of blebs lead to effective cross-presentation of MART-1 to specific CD8+ effector T cells.
1166	25870600	There were no remaining BCG bacilli, and scarce CD4(+) and Foxp3(+) T cells were determined.
1167	25870600	Some CD11c(+) cells proliferated; most of them contained intracellular MART-1 Ag, and some interacted with CD8(+) lymphocytes.
1168	26002978	In this study, using the novel NTA-His tag-containing multimer technology, we quantified the TCR:pMHC dissociation rates (koff) of tumor-specific vaccine-induced CD8 T cell clones (n = 139) derived from seven melanoma patients vaccinated with IFA, CpG, and the native/EAA or analog/ELA Melan-A(MART-1)(26-35) peptide, binding with low or high affinity to MHC, respectively.
1169	26049546	Following short-term (14 d) culture activation with anti-CD3/anti-CD28 microbeads and expansion in low concentrations of IL-2, the melanoma-draining lymph node (MDLN) cells were ∼ 60% CD4-activated and ∼ 40% CD8-activated T cells.
1170	26049546	The activated MDLN cells demonstrated reactivity in response to overlapping peptides spanning the sequence of 4 different known melanoma antigens MAGEA1, Melan-A/MART-1, NY-ESO-1, and Prame/OIP4, suggesting the presence of melanoma-specific T cells.
1171	26049546	Although prior human studies have demonstrated the immune responses within melanoma vaccine-draining lymph nodes, this study presents evidence for the first time that naturally occurring human MDLN samples contain melanoma-experienced CD4 and CD8 T cells that can be readily cultured and expanded to mediate protective immune responses both in vitro and in vivo in a human melanoma xenograft model.