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Gene Information

Gene symbol: SILV

Gene name: silver homolog (mouse)

HGNC ID: 10880

Related Genes

# Gene Symbol Number of hits
1 ADH1A 1 hits
2 AFP 1 hits
3 ALB 1 hits
4 ANKRD36B 1 hits
5 APOE 1 hits
6 BIRC5 1 hits
7 CCL21 1 hits
8 CCL5 1 hits
9 CD14 1 hits
10 CD209 1 hits
11 CD27 1 hits
12 CD34 1 hits
13 CD4 1 hits
14 CD40 1 hits
15 CD40LG 1 hits
16 CD58 1 hits
17 CD70 1 hits
18 CD80 1 hits
19 CD83 1 hits
20 CD86 1 hits
21 CD8A 1 hits
22 CSF1 1 hits
23 CSF2 1 hits
24 CTAG1B 1 hits
25 CTLA4 1 hits
26 CTNNB1 1 hits
27 CYP1B1 1 hits
28 DCT 1 hits
29 DPEP1 1 hits
30 ERBB2 1 hits
31 FCAMR 1 hits
32 FGF5 1 hits
33 GPC3 1 hits
34 HLA-A 1 hits
35 HLA-DRB1 1 hits
36 HLA-DRB5 1 hits
37 HOXD13 1 hits
38 ICAM1 1 hits
39 IFNA1 1 hits
40 IFNG 1 hits
41 IL12A 1 hits
42 IL18 1 hits
43 IL2 1 hits
44 INS 1 hits
45 JAG1 1 hits
46 JUP 1 hits
47 LTB 1 hits
48 MAA 1 hits
49 MAGEA1 1 hits
50 MAGEA10 1 hits
51 MAGEA12 1 hits
52 MAGEA2 1 hits
53 MAGEA3 1 hits
54 MAGEA4 1 hits
55 MAGEA6 1 hits
56 MAGEC2 1 hits
57 MC1R 1 hits
58 MCAM 1 hits
59 MCO 1 hits
60 MECP2 1 hits
61 MKI67 1 hits
62 MLANA 1 hits
63 MSTP1 1 hits
64 NGFR 1 hits
65 OSM 1 hits
66 PDXP 1 hits
67 PSG2 1 hits
68 RANBP2 1 hits
69 RPS27A 1 hits
70 S100A1 1 hits
71 SEPT4 1 hits
72 SLC22A7 1 hits
73 SP110 1 hits
74 TERT 1 hits
75 TFRC 1 hits
76 TH1L 1 hits
77 TLR9 1 hits
78 TNFRSF18 1 hits
79 TP53 1 hits
80 TPBG 1 hits
81 TRNAP1 1 hits
82 TRNAP2 1 hits
83 TYR 1 hits
84 TYRP1 1 hits
85 XCL1 1 hits
86 ZMYND10 1 hits

Related Sentences

# PMID Sentence
1 7667256 Untransfected L cells and L cells transfected with tyrosinase-related protein 1, TRP-1(gp75), were nonreactive.
2 7667256 The expression pattern of three melanosome-associated proteins--tyrosinase, TRP-1(gp75), and gp100--in melanoma was also compared.
3 7667256 Tyrosinase and gp100 are expressed in a higher percentage of melanomas than TRP-1(gp75), and the expression of these three antigens was discordant.
4 7667256 Tyrosinase expression within individual tumor specimen is usually homogenous, distinctly different from the commonly observed heterogeneous pattern of gp100 expression.
5 7667256 Untransfected L cells and L cells transfected with tyrosinase-related protein 1, TRP-1(gp75), were nonreactive.
6 7667256 The expression pattern of three melanosome-associated proteins--tyrosinase, TRP-1(gp75), and gp100--in melanoma was also compared.
7 7667256 Tyrosinase and gp100 are expressed in a higher percentage of melanomas than TRP-1(gp75), and the expression of these three antigens was discordant.
8 7667256 Tyrosinase expression within individual tumor specimen is usually homogenous, distinctly different from the commonly observed heterogeneous pattern of gp100 expression.
9 8543823 Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy.
10 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.
11 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.
12 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.
13 8543823 Depletion of CD8+ but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice eliminated the protective effect.
14 8543823 Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy.
15 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.
16 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.
17 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.
18 8543823 Depletion of CD8+ but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice eliminated the protective effect.
19 8543823 Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy.
20 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.
21 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.
22 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.
23 8543823 Depletion of CD8+ but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice eliminated the protective effect.
24 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.
25 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.
26 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.
27 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.
28 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.
29 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.
30 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.
31 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.
32 8690525 Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo.
33 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.
34 8690525 Enhanced DTH reactions and CD8+ CTL responses were observed after treatment with systemic GM-CSF.
35 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.
36 8811494 Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.
37 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.
38 8811494 One cell line did not express MART-1 or gp100.
39 8811494 None of the nonmelanoma cancer lines tested stained for MART-1 or gp100.
40 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.
41 8811494 Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.
42 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.
43 8811494 One cell line did not express MART-1 or gp100.
44 8811494 None of the nonmelanoma cancer lines tested stained for MART-1 or gp100.
45 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.
46 8811494 Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.
47 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.
48 8811494 One cell line did not express MART-1 or gp100.
49 8811494 None of the nonmelanoma cancer lines tested stained for MART-1 or gp100.
50 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.
51 8811494 Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.
52 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.
53 8811494 One cell line did not express MART-1 or gp100.
54 8811494 None of the nonmelanoma cancer lines tested stained for MART-1 or gp100.
55 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.
56 8811494 Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.
57 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.
58 8811494 One cell line did not express MART-1 or gp100.
59 8811494 None of the nonmelanoma cancer lines tested stained for MART-1 or gp100.
60 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.
61 8840994 Immunization against epitopes in the human melanoma antigen gp100 following patient immunization with synthetic peptides.
62 9101410 Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100.
63 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.
64 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.
65 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.
66 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.
67 9101410 Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100.
68 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.
69 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.
70 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.
71 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.
72 9101410 Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100.
73 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.
74 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.
75 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.
76 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.
77 9101410 Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100.
78 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.
79 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.
80 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.
81 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.
82 9101410 Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100.
83 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.
84 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.
85 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.
86 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.
87 9131386 Immunobiology of human melanoma antigens MART-1 and gp100 and their use for immuno-gene therapy.
88 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.
89 9131386 Immunobiology of human melanoma antigens MART-1 and gp100 and their use for immuno-gene therapy.
90 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.
91 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.
92 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.
93 9396616 Pmel 17 and Melan A have led to vaccines developed against differentiation antigens expressed in other solid tumors.
94 9396616 Similarly HER2/neu and mucin overexpression in breast cancer represent promising targets.
95 9419446 As an example, screening existent immunity in human melanoma has identified responses to nonmutated self proteins: MAGE, MART, gp100, and tyrosinase.
96 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.
97 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.
98 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.
99 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.
100 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.
101 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.
102 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.
103 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.
104 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.
105 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.
106 9637766 After four to five weekly stimulations of bulk PBLs with DC/gp100 or DC/lysates, the cultures were enriched with CD3+ T-cells and exhibited one of three phenotypic and functional patterns: (1) Predominant expression of CD8+ and MHC class I-restricted CTLs which displayed strong lytic activity against melanoma cells and T2 cells loaded with the gp100 peptide, (2) mixed CD4+/CD8+ phenotype and weak lytic activity, or (3) nonlytic and predominantly CD4+ cultures.
107 9670040 Although a recombinant vaccinia virus (rVV) encoding the mouse homologue of gp100 was nonimmunogenic, immunization of normal C57BL/6 mice with the rVV encoding the human gp100 elicited a specific CD8(+) T cell response.
108 9670040 The ability to induce specific T cells with human but not mouse gp100 resulted from differences within the major histocompatibility complex (MHC) class I-restricted epitope and not from differences elsewhere in the molecule, as was evidenced by experiments in which mice were immunized with rVV containing minigenes encoding these epitopes.
109 9670040 Although a recombinant vaccinia virus (rVV) encoding the mouse homologue of gp100 was nonimmunogenic, immunization of normal C57BL/6 mice with the rVV encoding the human gp100 elicited a specific CD8(+) T cell response.
110 9670040 The ability to induce specific T cells with human but not mouse gp100 resulted from differences within the major histocompatibility complex (MHC) class I-restricted epitope and not from differences elsewhere in the molecule, as was evidenced by experiments in which mice were immunized with rVV containing minigenes encoding these epitopes.
111 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.
112 9692858 The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16.
113 9692858 Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues.
114 9692858 Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens.
115 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.
116 9692858 The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16.
117 9692858 Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues.
118 9692858 Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens.
119 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.
120 9692858 The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16.
121 9692858 Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues.
122 9692858 Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens.
123 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.
124 9692858 The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16.
125 9692858 Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues.
126 9692858 Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens.
127 9764850 To assess antibody responses to potential melanoma/melanocyte autoantigens, the open-reading frame sequences of tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, and melanoma-associated glycoprotein antigen family (gp100/pmel17) genes were cloned and expressed as recombinant proteins in E. coli.
128 9816214 Specific CD8(+) CTL recognition of melanoma requires expression of MHC class I molecules as well as melanoma-associated peptide epitopes.
129 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.
130 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.
131 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.
132 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.
133 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.
134 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.
135 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.
136 9862627 Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens.
137 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.
138 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).
139 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.
140 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.
141 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).
142 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.
143 9862734 Although cDNAs encoding the previously identified melanoma Ags, tyrosinase and gp100, were isolated, these TIL were found to recognize previously unidentified peptides.
144 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.
145 10232365 A DNA vaccine has been analyzed here against malignant melanoma encoding gp100/pmel17, a melanoma-associated antigen.
146 10363968 To study the induction of anti-"self" CD8+ T-cell reactivity against the tumor antigen gp100, we used a mouse transgenic for a chimeric HLA-A*0201/H-2 Kb molecule (A2/Kb).
147 10363968 Immunogens containing the "anchor-fixed" modification elicited anti-self CD8+ T cells specific for the wild-type gp100(209-217) peptide pulsed onto target cells.
148 10363968 To study the induction of anti-"self" CD8+ T-cell reactivity against the tumor antigen gp100, we used a mouse transgenic for a chimeric HLA-A*0201/H-2 Kb molecule (A2/Kb).
149 10363968 Immunogens containing the "anchor-fixed" modification elicited anti-self CD8+ T cells specific for the wild-type gp100(209-217) peptide pulsed onto target cells.
150 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.
151 10388087 Instead, new vaccines like MART-1, gp100, p53 and ras peptides are targeting the cancer cell's ability to evade immune surveillance.
152 10417764 Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
153 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.
154 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.
155 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).
156 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.
157 10417764 Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
158 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.
159 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.
160 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).
161 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.
162 10417764 Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
163 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.
164 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.
165 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).
166 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.
167 10417764 Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
168 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.
169 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.
170 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).
171 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.
172 10417764 Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
173 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.
174 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.
175 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).
176 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.
177 10449616 In particular, no reactivity was found in sera from protected mice against tyrosinase-related protein 2 (TRP-2), either stably expressed in a non-melanoma cell line or obtained by in vitro transcription-translation, or against tyrosinase, TRP-1 and gp100 antigens immunoprecipitated from B16 cells.
178 10508491 Murine dendritic cells transfected with human GP100 elicit both antigen-specific CD8(+) and CD4(+) T-cell responses and are more effective than DNA vaccines at generating anti-tumor immunity.
179 10508491 In this report, we have used liposome-mediated gene transfer to examine the ability of plasmid DNA encoding the human melanoma-associated antigen gp100 to elicit CD8(+) and CD4(+) T-cell responses.
180 10508491 Antibody-mediated T-cell subset depletion experiments demonstrate that induction of CTLs in vivo is dependent on both CD4(+) and CD8(+) T cells.
181 10566900 The human melanoma-associated antigen gp100 mRNA was synthesized in vitro by pSFV3 vector and encapsulated in HVJ-liposomes.
182 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).
183 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.
184 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.
185 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.
186 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.
187 10725708 CD4+ T cells play a central role in the induction and persistence of CD8+ T cells in several models of autoimmune and infectious disease.
188 10725708 To identify a gp100 epitope restricted by the MHC class II allele with the highest prevalence in patients with malignant melanoma (HLA-DRB1*0401), we immunized mice transgenic for a chimeric human-mouse class II molecule (DR4-IE) with recombinant human gp100 protein.
189 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.
190 10752474 All four are deficient in expression of the melanocytic differentiation proteins (MDP) tyrosinase, Pme117/gp100, gp75/ trp-1, and MART-1/Melan-A.
191 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.
192 10752474 All four are deficient in expression of the melanocytic differentiation proteins (MDP) tyrosinase, Pme117/gp100, gp75/ trp-1, and MART-1/Melan-A.
193 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.
194 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.
195 10779556 We demonstrated that peripheral T cell tolerance toward murine melanoma self-antigens gp100 and TRP-2 can be broken by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to minigenes encoding peptide epitopes gp100(25-33) and TRP-2(181-188).
196 10779556 These epitopes contain dominant anchor residues for MHC class I antigen alleles H-2D(b) and H-2K(b), respectively.
197 10779556 Tumor-protective immunity was mediated by MHC class I antigen-restricted CD8(+) T cells that secreted T(H)1 cytokine IFN-gamma and induced tumor rejection and growth suppression after a lethal challenge with B16G3. 26 murine melanoma cells.
198 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.
199 10916759 Furthermore, DC-like function can be elicited from peripheral blood monocytes cultured in vitro with interleukin-4 and granulocyte-macrophage colony-stimulating factor.
200 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.
201 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.
202 10933943 In this study, we tested the efficacy of adenoviral vectors encoding human gp100 (Ad2/hugp100), murine gp100 (Ad2/mugp100), or murine TRP-2 (Ad2/muTRP-2) for their ability to elicit a specific cellular immune response and inhibit the growth of B16 melanoma tumor cells in the mouse.
203 10994477 These antigens include MAGE 1 and 3, tyrosinase, MelanA/MART-1 and gp100.
204 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.
205 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.
206 11092048 The vaccine contains multiple melanoma-associated antigens including MART-1, MAGE-3, tyrosinase and gp100.
207 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.
208 11092048 The vaccine contains multiple melanoma-associated antigens including MART-1, MAGE-3, tyrosinase and gp100.
209 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.
210 11221870 Therapeutic tumor immunity induced by polyimmunization with melanoma antigens gp100 and TRP-2.
211 11221870 Splenocytes from combination-immunized animals killed syngeneic targets loaded with peptides derived from both gp100 and TRP-2.
212 11221870 Therapeutic tumor immunity induced by polyimmunization with melanoma antigens gp100 and TRP-2.
213 11221870 Splenocytes from combination-immunized animals killed syngeneic targets loaded with peptides derived from both gp100 and TRP-2.
214 11309346 Effective particle-mediated vaccination against mouse melanoma by coadministration of plasmid DNA encoding Gp100 and granulocyte-macrophage colony-stimulating factor.
215 11309346 Mice were immunized with a plasmid cDNA coding for the human melanoma-associated antigen, gp100.
216 11309346 Co-delivery of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmid together with the gp100 plasmid consistently resulted in a greater level of protection from tumor challenge.
217 11309346 The inclusion of the GM-CSF plasmid with the gp100 DNA vaccine allowed a reduction in the gp100 plasmid dose required for antitumor efficacy.
218 11309346 Tumor protection induced by the gp100 + GM-CSF gene combination was T cell mediated, because it was abrogated in vaccinated mice treated with anti-CD4 and anti-CD8 monoclonal antibodies.
219 11309346 In addition, administration of the gp100 + GM-CSF DNA vaccine to mice bearing established 7-day tumors resulted in significant suppression of tumor growth.
220 11309346 These results indicate that inclusion of GM-CSF DNA augments the efficacy of particle-mediated vaccination with gp100 DNA, and this form of combined gp100 + GM-CSF DNA vaccine warrants clinical evaluation in melanoma patients.
221 11309346 Effective particle-mediated vaccination against mouse melanoma by coadministration of plasmid DNA encoding Gp100 and granulocyte-macrophage colony-stimulating factor.
222 11309346 Mice were immunized with a plasmid cDNA coding for the human melanoma-associated antigen, gp100.
223 11309346 Co-delivery of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmid together with the gp100 plasmid consistently resulted in a greater level of protection from tumor challenge.
224 11309346 The inclusion of the GM-CSF plasmid with the gp100 DNA vaccine allowed a reduction in the gp100 plasmid dose required for antitumor efficacy.
225 11309346 Tumor protection induced by the gp100 + GM-CSF gene combination was T cell mediated, because it was abrogated in vaccinated mice treated with anti-CD4 and anti-CD8 monoclonal antibodies.
226 11309346 In addition, administration of the gp100 + GM-CSF DNA vaccine to mice bearing established 7-day tumors resulted in significant suppression of tumor growth.
227 11309346 These results indicate that inclusion of GM-CSF DNA augments the efficacy of particle-mediated vaccination with gp100 DNA, and this form of combined gp100 + GM-CSF DNA vaccine warrants clinical evaluation in melanoma patients.
228 11309346 Effective particle-mediated vaccination against mouse melanoma by coadministration of plasmid DNA encoding Gp100 and granulocyte-macrophage colony-stimulating factor.
229 11309346 Mice were immunized with a plasmid cDNA coding for the human melanoma-associated antigen, gp100.
230 11309346 Co-delivery of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmid together with the gp100 plasmid consistently resulted in a greater level of protection from tumor challenge.
231 11309346 The inclusion of the GM-CSF plasmid with the gp100 DNA vaccine allowed a reduction in the gp100 plasmid dose required for antitumor efficacy.
232 11309346 Tumor protection induced by the gp100 + GM-CSF gene combination was T cell mediated, because it was abrogated in vaccinated mice treated with anti-CD4 and anti-CD8 monoclonal antibodies.
233 11309346 In addition, administration of the gp100 + GM-CSF DNA vaccine to mice bearing established 7-day tumors resulted in significant suppression of tumor growth.
234 11309346 These results indicate that inclusion of GM-CSF DNA augments the efficacy of particle-mediated vaccination with gp100 DNA, and this form of combined gp100 + GM-CSF DNA vaccine warrants clinical evaluation in melanoma patients.
235 11309346 Effective particle-mediated vaccination against mouse melanoma by coadministration of plasmid DNA encoding Gp100 and granulocyte-macrophage colony-stimulating factor.
236 11309346 Mice were immunized with a plasmid cDNA coding for the human melanoma-associated antigen, gp100.
237 11309346 Co-delivery of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmid together with the gp100 plasmid consistently resulted in a greater level of protection from tumor challenge.
238 11309346 The inclusion of the GM-CSF plasmid with the gp100 DNA vaccine allowed a reduction in the gp100 plasmid dose required for antitumor efficacy.
239 11309346 Tumor protection induced by the gp100 + GM-CSF gene combination was T cell mediated, because it was abrogated in vaccinated mice treated with anti-CD4 and anti-CD8 monoclonal antibodies.
240 11309346 In addition, administration of the gp100 + GM-CSF DNA vaccine to mice bearing established 7-day tumors resulted in significant suppression of tumor growth.
241 11309346 These results indicate that inclusion of GM-CSF DNA augments the efficacy of particle-mediated vaccination with gp100 DNA, and this form of combined gp100 + GM-CSF DNA vaccine warrants clinical evaluation in melanoma patients.
242 11309346 Effective particle-mediated vaccination against mouse melanoma by coadministration of plasmid DNA encoding Gp100 and granulocyte-macrophage colony-stimulating factor.
243 11309346 Mice were immunized with a plasmid cDNA coding for the human melanoma-associated antigen, gp100.
244 11309346 Co-delivery of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmid together with the gp100 plasmid consistently resulted in a greater level of protection from tumor challenge.
245 11309346 The inclusion of the GM-CSF plasmid with the gp100 DNA vaccine allowed a reduction in the gp100 plasmid dose required for antitumor efficacy.
246 11309346 Tumor protection induced by the gp100 + GM-CSF gene combination was T cell mediated, because it was abrogated in vaccinated mice treated with anti-CD4 and anti-CD8 monoclonal antibodies.
247 11309346 In addition, administration of the gp100 + GM-CSF DNA vaccine to mice bearing established 7-day tumors resulted in significant suppression of tumor growth.
248 11309346 These results indicate that inclusion of GM-CSF DNA augments the efficacy of particle-mediated vaccination with gp100 DNA, and this form of combined gp100 + GM-CSF DNA vaccine warrants clinical evaluation in melanoma patients.
249 11309346 Effective particle-mediated vaccination against mouse melanoma by coadministration of plasmid DNA encoding Gp100 and granulocyte-macrophage colony-stimulating factor.
250 11309346 Mice were immunized with a plasmid cDNA coding for the human melanoma-associated antigen, gp100.
251 11309346 Co-delivery of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmid together with the gp100 plasmid consistently resulted in a greater level of protection from tumor challenge.
252 11309346 The inclusion of the GM-CSF plasmid with the gp100 DNA vaccine allowed a reduction in the gp100 plasmid dose required for antitumor efficacy.
253 11309346 Tumor protection induced by the gp100 + GM-CSF gene combination was T cell mediated, because it was abrogated in vaccinated mice treated with anti-CD4 and anti-CD8 monoclonal antibodies.
254 11309346 In addition, administration of the gp100 + GM-CSF DNA vaccine to mice bearing established 7-day tumors resulted in significant suppression of tumor growth.
255 11309346 These results indicate that inclusion of GM-CSF DNA augments the efficacy of particle-mediated vaccination with gp100 DNA, and this form of combined gp100 + GM-CSF DNA vaccine warrants clinical evaluation in melanoma patients.
256 11340576 We vaccinated stage IV melanoma patients with a mixture of gp100 and tyrosinase peptides restricted by HLA-A1 (DAEKSDICTDEY), HLA-A2 (YLEPGPVTA and YMDGTMSQV) and HLA-A3 (ALLAVGATK) in an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
257 11340576 CTLs expanded from the SIN lysed melanoma cells naturally expressing tyrosinase or gp100.
258 11340576 We vaccinated stage IV melanoma patients with a mixture of gp100 and tyrosinase peptides restricted by HLA-A1 (DAEKSDICTDEY), HLA-A2 (YLEPGPVTA and YMDGTMSQV) and HLA-A3 (ALLAVGATK) in an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
259 11340576 CTLs expanded from the SIN lysed melanoma cells naturally expressing tyrosinase or gp100.
260 11357937 Gp100 is a human melanoma-associated antigen (hgp100) with a highly homologous mouse counterpart, pmel17/gp100 (mgp100), that is expressed in melanocytes and highly tumorigenic B16 melanoma cells.
261 11357937 Depletion of T cell subsets revealed that the protective effect observed after vaccination with plasmid DNA was mediated by CD4+ and CD8+ T cells, while protection following vaccination with DNA encoding hgp100 in combination with peptides appears to depend on CD4+ T cells only.
262 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.
263 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.
264 11507070 We demonstrate that a mouse-human chimeric anti-ganglioside GD2-interleukin (IL)-2 fusion protein (ch14.18-IL2) substantially amplifies tumor-protective immunity against murine melanoma induced by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to murine melanoma peptide epitopes gp100(25-35) and TRP-2(181-188).
265 11507070 The tumor-protective immunity was mediated by MHC class I antigen- restricted CD8(+) T cells together with CD4(+) T cell help, which was required only for tumor cell killing in the effector phase of the immune response.
266 11507070 The immunological mechanisms involved in this antitumor effect were suggested by a decisively increased secretion of tumor necrosis factor alpha TNFTnTNa and IFN-gamma from CD4(+) and CD8(+) T cells and a markedly up-regulated expression on CD8(+) T cells of high-affinity IL-2 receptor alpha chain (CD25), costimulatory molecule CD28, and adhesion molecule lymphocyte function-associated antigen-2 (LFA-2/CD2).
267 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.
268 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.
269 11514604 There was no evidence of reactivity to the melanocyte antigens gp100, tyrosinase, Mart1/MelanA, or TRP1.
270 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.
271 11519046 In this study we document the surfacing of systemic immune reactivity toward a cryptic epitope from the MAGE-12 gene (MAGE-12:170-178), after temporary regression of a single melanoma metastasis, in response to gp100/PMel17-specific vaccination.
272 11519046 Surfacing of MAGE-12 specificity occurred in association with loss of gp100/PMel 17 targeted by the vaccine.
273 11519046 In this study we document the surfacing of systemic immune reactivity toward a cryptic epitope from the MAGE-12 gene (MAGE-12:170-178), after temporary regression of a single melanoma metastasis, in response to gp100/PMel17-specific vaccination.
274 11519046 Surfacing of MAGE-12 specificity occurred in association with loss of gp100/PMel 17 targeted by the vaccine.
275 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.
276 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.
277 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.
278 11684122 We have developed a whole cell enzyme-linked immunosorbent assay (ELISA) that detects the melanoma antigens gp100 and S-100 in tumor samples from patients with metastatic melanoma and the antigen CA 125 in tumor samples from patients with ovarian carcinoma.
279 11730848 C57BL/6 mice were immunized with an adenoviral vector encoding the melanoma antigen gp100 (Ad2/gp100) or were left untreated.
280 11730848 Blood and spleen cells were restimulated with either a peptide containing the dominant gp100 MHC Class I-restricted epitope, gp100(25-33), or a negative control peptide containing an irrelevant Class I-restricted epitope from ovalbumin.
281 11730848 C57BL/6 mice were immunized with an adenoviral vector encoding the melanoma antigen gp100 (Ad2/gp100) or were left untreated.
282 11730848 Blood and spleen cells were restimulated with either a peptide containing the dominant gp100 MHC Class I-restricted epitope, gp100(25-33), or a negative control peptide containing an irrelevant Class I-restricted epitope from ovalbumin.
283 11730853 CD40 ligand and lipopolysaccharide enhance the in vitro generation of melanoma-reactive T-cells.
284 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).
285 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.
286 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.
287 11742496 gp100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+T cells.
288 11742496 In order to identify the tumour epitopes recognized by tumour-reactive human CD4+ T cells, we combined the use of an HLA-DR4/peptide binding algorithm with an IFN-gamma ELISPOT assay.
289 11742496 Two known and three novel CD4+ T cell epitopes derived from the gp 100/pmel17 and tyrosinase melanocyte-associated antigens were confirmed or identified.
290 11742496 gp100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+T cells.
291 11742496 In order to identify the tumour epitopes recognized by tumour-reactive human CD4+ T cells, we combined the use of an HLA-DR4/peptide binding algorithm with an IFN-gamma ELISPOT assay.
292 11742496 Two known and three novel CD4+ T cell epitopes derived from the gp 100/pmel17 and tyrosinase melanocyte-associated antigens were confirmed or identified.
293 11863419 We developed a polyvalent melanoma gene vaccine using a plasmid vector to deliver the immunogenic human melanoma-associated antigens (MAAs) gp100 and TRP-2.
294 11863419 Although both i.m. and i.n. immunization induced Th1 (T helper) and Th2 cell responses to gp100 and TRP2, the i.m. route induced a better Th1 response.
295 11863419 We developed a polyvalent melanoma gene vaccine using a plasmid vector to deliver the immunogenic human melanoma-associated antigens (MAAs) gp100 and TRP-2.
296 11863419 Although both i.m. and i.n. immunization induced Th1 (T helper) and Th2 cell responses to gp100 and TRP2, the i.m. route induced a better Th1 response.
297 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.
298 11912169 The ability to load irradiated tumor cells was reproduced in two analogous human melanoma models using melanoma cell lines expressing gp100 and CTL clones specific for a gp100 melanoma antigen.
299 11973635 Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100.
300 11973635 In this study, Lptn and/or melanoma-associated antigen gp100 were transfected into mouse bone marrow-derived DC, which were used as vaccines in B16 melanoma model.
301 11973635 Immunization of C57BL/6 mice with DC adenovirally cotransfected with Lptn and gp100 (Lptn/gp100-DC) could enhance the cytotoxicities of CTL and NK cells, increase the production of IL-2 and interferon-gamma significantly, as compared with immunization with gp100-DC, Lptn-DC, LacZ-DC, DC or PBS counterparts.
302 11973635 In vivo depletion analysis demonstrated that CD8(+) T cells are the predominant T cell subset responsible for the antitumor effect of Lptn/gp100-DC and CD4(+) T cells were necessary in the induction phase of tumor rejection, while NK cells were less important although they participated in the antitumor response either in the induction phase or in the effector phase.
303 11973635 Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100.
304 11973635 In this study, Lptn and/or melanoma-associated antigen gp100 were transfected into mouse bone marrow-derived DC, which were used as vaccines in B16 melanoma model.
305 11973635 Immunization of C57BL/6 mice with DC adenovirally cotransfected with Lptn and gp100 (Lptn/gp100-DC) could enhance the cytotoxicities of CTL and NK cells, increase the production of IL-2 and interferon-gamma significantly, as compared with immunization with gp100-DC, Lptn-DC, LacZ-DC, DC or PBS counterparts.
306 11973635 In vivo depletion analysis demonstrated that CD8(+) T cells are the predominant T cell subset responsible for the antitumor effect of Lptn/gp100-DC and CD4(+) T cells were necessary in the induction phase of tumor rejection, while NK cells were less important although they participated in the antitumor response either in the induction phase or in the effector phase.
307 11973635 Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100.
308 11973635 In this study, Lptn and/or melanoma-associated antigen gp100 were transfected into mouse bone marrow-derived DC, which were used as vaccines in B16 melanoma model.
309 11973635 Immunization of C57BL/6 mice with DC adenovirally cotransfected with Lptn and gp100 (Lptn/gp100-DC) could enhance the cytotoxicities of CTL and NK cells, increase the production of IL-2 and interferon-gamma significantly, as compared with immunization with gp100-DC, Lptn-DC, LacZ-DC, DC or PBS counterparts.
310 11973635 In vivo depletion analysis demonstrated that CD8(+) T cells are the predominant T cell subset responsible for the antitumor effect of Lptn/gp100-DC and CD4(+) T cells were necessary in the induction phase of tumor rejection, while NK cells were less important although they participated in the antitumor response either in the induction phase or in the effector phase.
311 12056962 Hypopigmentation associated with an adenovirus-mediated gp100/MART-1-transduced dendritic cell vaccine for metastatic melanoma.
312 12124806 Immunization of these HLA-A2402/K(b)-transgenic mice with various known HLA-A24-restricted immunodominant cancer CTL epitope peptides derived from gp100, MAGE-1, MAGE-3, Her2/neu, CEA and TERT induced HLA-A24-restricted, peptide-specific CTLs.
313 12124806 Staining with HLA tetramers showed that the cytotoxic activity induced by immunizing with PSA(152-160) in HLA-A2402/K(b) transgenic mice was HLA-A2402-restricted and CD8-dependent.
314 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.
315 12192536 Expression of melanoma-associated antigens (MART-1, gp100) in hybrid cells was determined by reverse transcription-polymerase chain reaction (RT-PCR).
316 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.
317 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.
318 12192536 Expression of melanoma-associated antigens (MART-1, gp100) in hybrid cells was determined by reverse transcription-polymerase chain reaction (RT-PCR).
319 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.
320 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.
321 12192536 Expression of melanoma-associated antigens (MART-1, gp100) in hybrid cells was determined by reverse transcription-polymerase chain reaction (RT-PCR).
322 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.
323 12427970 Forty-three infusions of MART1MelanA-specific or gp100-specific CD8+ T cell clones were administered to 10 patients.
324 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.
325 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.
326 12734382 In contrast, DCs could not cross-present MHC class I-restricted epitopes after exogenously loading with gp100 protein.
327 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.
328 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.
329 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.
330 12734382 In contrast, DCs could not cross-present MHC class I-restricted epitopes after exogenously loading with gp100 protein.
331 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.
332 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.
333 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.
334 12734382 In contrast, DCs could not cross-present MHC class I-restricted epitopes after exogenously loading with gp100 protein.
335 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.
336 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.
337 12750279 Targeted immunotherapy using reconstituted chaperone complexes of heat shock protein 110 and melanoma-associated antigen gp100.
338 12750279 This report defines a novel approach to heat shock protein vaccine formulation that takes advantage of the chaperoning property of heat shock protein hsp110 to efficiently bind a large protein substrate (specifically, human melanoma-associated antigen gp100) during heat shock.
339 12750279 Immunization with the hsp110-gp100 complex protected mice against subsequent challenge with human gp100-transduced B16 melanoma, which involves both CD4(+) and CD8(+) T-cell populations.
340 12750279 Targeted immunotherapy using reconstituted chaperone complexes of heat shock protein 110 and melanoma-associated antigen gp100.
341 12750279 This report defines a novel approach to heat shock protein vaccine formulation that takes advantage of the chaperoning property of heat shock protein hsp110 to efficiently bind a large protein substrate (specifically, human melanoma-associated antigen gp100) during heat shock.
342 12750279 Immunization with the hsp110-gp100 complex protected mice against subsequent challenge with human gp100-transduced B16 melanoma, which involves both CD4(+) and CD8(+) T-cell populations.
343 12750279 Targeted immunotherapy using reconstituted chaperone complexes of heat shock protein 110 and melanoma-associated antigen gp100.
344 12750279 This report defines a novel approach to heat shock protein vaccine formulation that takes advantage of the chaperoning property of heat shock protein hsp110 to efficiently bind a large protein substrate (specifically, human melanoma-associated antigen gp100) during heat shock.
345 12750279 Immunization with the hsp110-gp100 complex protected mice against subsequent challenge with human gp100-transduced B16 melanoma, which involves both CD4(+) and CD8(+) T-cell populations.
346 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.
347 12937899 To improve the antitumor effect of DC vaccine, Th1-biasing cytokine interleukin (IL) 18 and melanoma-associated antigen gp100 were cotransfected into bone marrow-derived DC (IL-18/gp100-DC), which were used as vaccine to induce the protective and therapeutic immunity in a B16 melanoma model.
348 12937899 Immunization with IL-18/gp100-DC resulted in tumor resistance in 87.5% of the mice challenged with B16 cells; however, 12.5% and 25% of mice immunized with gp100 gene-modified DC (gp100-DC) or IL-18 gene-modified DC (IL-18-DC) were tumor free, respectively.
349 12937899 Immune cell depletion experiments identified that CD4(+) T cells also played an important role in the priming phase of antitumor immunity and CD8(+) T lymphocytes were the primary effectors. gp100-specific CTL response were induced most markedly in the tumor-bearing mice immunized with IL-18/gp100-DC.
350 12937899 Administration with such vaccine also significantly increased the production of Th1 cytokine (IL-2 and interferon-gamma) and induced infiltration of inflammatory cells inside and around the tumors.
351 12937899 These results indicate that immunization with DC vaccine coexpressing Th1 cytokine IL-18 and tumor antigen gene may be an effective strategy for a successful therapeutic vaccination.
352 12937899 To improve the antitumor effect of DC vaccine, Th1-biasing cytokine interleukin (IL) 18 and melanoma-associated antigen gp100 were cotransfected into bone marrow-derived DC (IL-18/gp100-DC), which were used as vaccine to induce the protective and therapeutic immunity in a B16 melanoma model.
353 12937899 Immunization with IL-18/gp100-DC resulted in tumor resistance in 87.5% of the mice challenged with B16 cells; however, 12.5% and 25% of mice immunized with gp100 gene-modified DC (gp100-DC) or IL-18 gene-modified DC (IL-18-DC) were tumor free, respectively.
354 12937899 Immune cell depletion experiments identified that CD4(+) T cells also played an important role in the priming phase of antitumor immunity and CD8(+) T lymphocytes were the primary effectors. gp100-specific CTL response were induced most markedly in the tumor-bearing mice immunized with IL-18/gp100-DC.
355 12937899 Administration with such vaccine also significantly increased the production of Th1 cytokine (IL-2 and interferon-gamma) and induced infiltration of inflammatory cells inside and around the tumors.
356 12937899 These results indicate that immunization with DC vaccine coexpressing Th1 cytokine IL-18 and tumor antigen gene may be an effective strategy for a successful therapeutic vaccination.
357 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.
358 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.
359 12973032 Thus, a single injection of CD34 HPC-derived DCs can lead to rapid immune response to CD4 epitopes or to melanoma antigens.
360 14502218 The aim of the present study is to demonstrate the predominance of ex vivo genetic DC manipulation using AdRGD in improving the efficacy of DC-based immunotherapy targeting gp100, a melanoma-associated antigen (MAA).
361 14502218 Furthermore, in vivo depletion analysis demonstrated that CD8(+) CTLs and NK cells were the predominant effector cells responsible for the anti-B16BL6 immunity induced by vaccination with AdRGD-gp100/mBM-DCs, and that helper function of CD4(+) T cells was necessary for sufficiently eliciting effector activity.
362 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.
363 14577912 Corresponding soluble peptides were used to boost responses and granulocyte-macrophage colony-stimulating factor was used as systemic adjuvant.
364 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.
365 14600790 DCs were produced from adherent cells in blood lymphocytes (monocytic DCs), grown in IL-4 and GM-CSF without a maturation step.
366 14609222 DCs were pulsed with MART1, tyrosinase, MAGE3, gp100 and Flu-MP peptides, and KLH.
367 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.
368 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.
369 14679014 In this study, we provide evidence that two common murine glioma cell lines (GL26 and GL261) express the melanoma antigens gp100 and tyrosinase-related protein 2 (TRP-2).
370 14679014 Lastly, mice that were prevaccinated with human gp100 and TRP-2 peptide-pulsed dendritic cells had significantly extended survival when challenged with tumor cells in the brain, resulting in >50% long-term survival.
371 14679014 In this study, we provide evidence that two common murine glioma cell lines (GL26 and GL261) express the melanoma antigens gp100 and tyrosinase-related protein 2 (TRP-2).
372 14679014 Lastly, mice that were prevaccinated with human gp100 and TRP-2 peptide-pulsed dendritic cells had significantly extended survival when challenged with tumor cells in the brain, resulting in >50% long-term survival.
373 15068853 CTLA-4 blockade enhanced B16 tumor rejection in mice immunized against the melanoma differentiation antigens tyrosinase-related protein 2 and gp100, and this effect was stronger when anti-CTLA-4 was administered with booster vaccinations.
374 15068853 CTLA-4 blockade also increased the T-cell responses to prostate-specific membrane antigen (PSMA) when given with the second or third vaccination.
375 15160996 In this study, we investigated the specific CTL-inducing activity of 5 HLA-A*2402-restricted peptides derived from gp100, tyrosinase, MAGE1, MAGE2 and MAGE3.
376 15235388 Immunization with melanoma-associated antigens was accomplished using recombinant adenovirus (Ad) vectors encoding human gp100 (Ad2/gp100) or murine TRP-2 (Ad2/mTRP-2).
377 15235388 A single dose of Ad2/gp100 or Ad2/mTRP-2 inhibited the growth of established subcutaneous B16 melanoma tumors in B cell-deficient but not wild-type C57BL/6 mice.
378 15235388 Immunization with melanoma-associated antigens was accomplished using recombinant adenovirus (Ad) vectors encoding human gp100 (Ad2/gp100) or murine TRP-2 (Ad2/mTRP-2).
379 15235388 A single dose of Ad2/gp100 or Ad2/mTRP-2 inhibited the growth of established subcutaneous B16 melanoma tumors in B cell-deficient but not wild-type C57BL/6 mice.
380 15256471 Using HLA-restricted tetramer staining, we identified a significant expansion in CD8+ antigen-specific T-cell clones against one or more of tumor-associated antigens MAGE-1, gp100, and HER-2 after DC vaccination in four of nine patients.
381 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).
382 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.
383 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.
384 15389286 Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12.
385 15389286 In the present study, in order to create a dendritic cell (DC)-based vaccine capable of positively skewing immune response toward a cellular immunity-dominant state, we analyzed immunological characteristics and vaccine efficacy of DCs cotransduced with melanoma-associated antigen (gp100) and IL-12 gene (gp100+IL12/DCs) by using RGD fiber-mutant adenovirus vector (AdRGD), which enables highly efficient gene transduction into DCs. gp100+IL12/DCs could simultaneously express cytoplasmic gp100 and secretory IL-12 at levels comparable to DCs transduced with each gene alone.
386 15389286 In comparison with DCs transduced with gp100 alone (gp100/DCs), upregulation of major histocompatibility complex class I, CD40, and CD86 molecules on the cell surface and more potent T-cell-stimulating ability for proliferation and interferon-gamma secretion were observed as characteristic changes in gp100+IL12/DCs.
387 15389286 In addition, administration of gp100+IL12/DCs, which were prepared by a relatively low dose of AdRGD-IL12, could induce more potent tumor-specific cellular immunity in the murine B16BL6 melanoma model than vaccination with gp100/DCs.
388 15389286 However, antitumor effect and B16BL6-specific cytotoxic T-lymphocyte activity in mice vaccinated with gp100+IL12/DCs diminished with increasing AdRGD-IL12 dose during gene transduction, and paralleled the decrease in presentation levels via MHC class I molecules for antigen transduced with another AdRGD.
389 15389286 Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12.
390 15389286 In the present study, in order to create a dendritic cell (DC)-based vaccine capable of positively skewing immune response toward a cellular immunity-dominant state, we analyzed immunological characteristics and vaccine efficacy of DCs cotransduced with melanoma-associated antigen (gp100) and IL-12 gene (gp100+IL12/DCs) by using RGD fiber-mutant adenovirus vector (AdRGD), which enables highly efficient gene transduction into DCs. gp100+IL12/DCs could simultaneously express cytoplasmic gp100 and secretory IL-12 at levels comparable to DCs transduced with each gene alone.
391 15389286 In comparison with DCs transduced with gp100 alone (gp100/DCs), upregulation of major histocompatibility complex class I, CD40, and CD86 molecules on the cell surface and more potent T-cell-stimulating ability for proliferation and interferon-gamma secretion were observed as characteristic changes in gp100+IL12/DCs.
392 15389286 In addition, administration of gp100+IL12/DCs, which were prepared by a relatively low dose of AdRGD-IL12, could induce more potent tumor-specific cellular immunity in the murine B16BL6 melanoma model than vaccination with gp100/DCs.
393 15389286 However, antitumor effect and B16BL6-specific cytotoxic T-lymphocyte activity in mice vaccinated with gp100+IL12/DCs diminished with increasing AdRGD-IL12 dose during gene transduction, and paralleled the decrease in presentation levels via MHC class I molecules for antigen transduced with another AdRGD.
394 15389286 Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12.
395 15389286 In the present study, in order to create a dendritic cell (DC)-based vaccine capable of positively skewing immune response toward a cellular immunity-dominant state, we analyzed immunological characteristics and vaccine efficacy of DCs cotransduced with melanoma-associated antigen (gp100) and IL-12 gene (gp100+IL12/DCs) by using RGD fiber-mutant adenovirus vector (AdRGD), which enables highly efficient gene transduction into DCs. gp100+IL12/DCs could simultaneously express cytoplasmic gp100 and secretory IL-12 at levels comparable to DCs transduced with each gene alone.
396 15389286 In comparison with DCs transduced with gp100 alone (gp100/DCs), upregulation of major histocompatibility complex class I, CD40, and CD86 molecules on the cell surface and more potent T-cell-stimulating ability for proliferation and interferon-gamma secretion were observed as characteristic changes in gp100+IL12/DCs.
397 15389286 In addition, administration of gp100+IL12/DCs, which were prepared by a relatively low dose of AdRGD-IL12, could induce more potent tumor-specific cellular immunity in the murine B16BL6 melanoma model than vaccination with gp100/DCs.
398 15389286 However, antitumor effect and B16BL6-specific cytotoxic T-lymphocyte activity in mice vaccinated with gp100+IL12/DCs diminished with increasing AdRGD-IL12 dose during gene transduction, and paralleled the decrease in presentation levels via MHC class I molecules for antigen transduced with another AdRGD.
399 15389286 Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12.
400 15389286 In the present study, in order to create a dendritic cell (DC)-based vaccine capable of positively skewing immune response toward a cellular immunity-dominant state, we analyzed immunological characteristics and vaccine efficacy of DCs cotransduced with melanoma-associated antigen (gp100) and IL-12 gene (gp100+IL12/DCs) by using RGD fiber-mutant adenovirus vector (AdRGD), which enables highly efficient gene transduction into DCs. gp100+IL12/DCs could simultaneously express cytoplasmic gp100 and secretory IL-12 at levels comparable to DCs transduced with each gene alone.
401 15389286 In comparison with DCs transduced with gp100 alone (gp100/DCs), upregulation of major histocompatibility complex class I, CD40, and CD86 molecules on the cell surface and more potent T-cell-stimulating ability for proliferation and interferon-gamma secretion were observed as characteristic changes in gp100+IL12/DCs.
402 15389286 In addition, administration of gp100+IL12/DCs, which were prepared by a relatively low dose of AdRGD-IL12, could induce more potent tumor-specific cellular immunity in the murine B16BL6 melanoma model than vaccination with gp100/DCs.
403 15389286 However, antitumor effect and B16BL6-specific cytotoxic T-lymphocyte activity in mice vaccinated with gp100+IL12/DCs diminished with increasing AdRGD-IL12 dose during gene transduction, and paralleled the decrease in presentation levels via MHC class I molecules for antigen transduced with another AdRGD.
404 15449035 The (MHC class I-restricted) peptides were from gp100, MART-1, tyrosinase, and MAGE-3.
405 15449035 The gp100 and MART-1 peptides had been modified to increase their immunogenicity.
406 15449035 The (MHC class I-restricted) peptides were from gp100, MART-1, tyrosinase, and MAGE-3.
407 15449035 The gp100 and MART-1 peptides had been modified to increase their immunogenicity.
408 15585842 To test whether tumor-reactive CD8(+) T cells specifically home to tumor, we assessed the trafficking of gp100-specific pmel-1 cells to large, vascularized tumors that express or do not express the target Ag.
409 15585842 Activation of tumor-specific CD8(+) pmel-1 T cells with IL-2 and vaccination with an altered peptide ligand caused regression of gp100-positive tumors (B16), but not gp100-negative tumors (methylcholanthrene 205), implanted on opposing flanks of the same mouse.
410 15585842 Most importantly, evidence for T cell function, as measured by production of IFN-gamma, release of perforin, and activation of caspase-3 in target cells, was confined to Ag-expressing tumor.
411 15585842 To test whether tumor-reactive CD8(+) T cells specifically home to tumor, we assessed the trafficking of gp100-specific pmel-1 cells to large, vascularized tumors that express or do not express the target Ag.
412 15585842 Activation of tumor-specific CD8(+) pmel-1 T cells with IL-2 and vaccination with an altered peptide ligand caused regression of gp100-positive tumors (B16), but not gp100-negative tumors (methylcholanthrene 205), implanted on opposing flanks of the same mouse.
413 15585842 Most importantly, evidence for T cell function, as measured by production of IFN-gamma, release of perforin, and activation of caspase-3 in target cells, was confined to Ag-expressing tumor.
414 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.
415 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.
416 15657293 CTLp's recognizing MAGE-C2 and gp100 antigens were already present before vaccination, but new clonotypes appeared afterwards.
417 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).
418 15728523 MAGE-A1-, MAGE-A10-, and gp100-derived peptides are immunogenic when combined with granulocyte-macrophage colony-stimulating factor and montanide ISA-51 adjuvant and administered as part of a multipeptide vaccine for melanoma.
419 15728523 We report in this study that at least three of these five peptides (MAGE-A1(96-104), MAGE-A10(254-262), and gp100(614-622)) are immunogenic when administered with GM-CSF in Montanide ISA-51 adjuvant.
420 15728523 Most importantly, tumor cell lines expressing the appropriate HLA-A restriction element and MAGE-A1, MAGE-A10, or gp100 proteins were lysed by corresponding CTL.
421 15728523 This report supports the continued use of the MAGE-A1(96-104), MAGE-A10(254-262), and gp100(614-622) epitopes in peptide-based melanoma vaccines and thus expands the list of immunogenic peptide Ags available for human use.
422 15728523 Cancer-testis Ags are expressed in multiple types of cancer; thus the MAGE-A1(96-104) and MAGE-A10(254-262) peptides may be considered for inclusion in vaccines against cancers of other histologic types, in addition to melanoma.
423 15728523 MAGE-A1-, MAGE-A10-, and gp100-derived peptides are immunogenic when combined with granulocyte-macrophage colony-stimulating factor and montanide ISA-51 adjuvant and administered as part of a multipeptide vaccine for melanoma.
424 15728523 We report in this study that at least three of these five peptides (MAGE-A1(96-104), MAGE-A10(254-262), and gp100(614-622)) are immunogenic when administered with GM-CSF in Montanide ISA-51 adjuvant.
425 15728523 Most importantly, tumor cell lines expressing the appropriate HLA-A restriction element and MAGE-A1, MAGE-A10, or gp100 proteins were lysed by corresponding CTL.
426 15728523 This report supports the continued use of the MAGE-A1(96-104), MAGE-A10(254-262), and gp100(614-622) epitopes in peptide-based melanoma vaccines and thus expands the list of immunogenic peptide Ags available for human use.
427 15728523 Cancer-testis Ags are expressed in multiple types of cancer; thus the MAGE-A1(96-104) and MAGE-A10(254-262) peptides may be considered for inclusion in vaccines against cancers of other histologic types, in addition to melanoma.
428 15728523 MAGE-A1-, MAGE-A10-, and gp100-derived peptides are immunogenic when combined with granulocyte-macrophage colony-stimulating factor and montanide ISA-51 adjuvant and administered as part of a multipeptide vaccine for melanoma.
429 15728523 We report in this study that at least three of these five peptides (MAGE-A1(96-104), MAGE-A10(254-262), and gp100(614-622)) are immunogenic when administered with GM-CSF in Montanide ISA-51 adjuvant.
430 15728523 Most importantly, tumor cell lines expressing the appropriate HLA-A restriction element and MAGE-A1, MAGE-A10, or gp100 proteins were lysed by corresponding CTL.
431 15728523 This report supports the continued use of the MAGE-A1(96-104), MAGE-A10(254-262), and gp100(614-622) epitopes in peptide-based melanoma vaccines and thus expands the list of immunogenic peptide Ags available for human use.
432 15728523 Cancer-testis Ags are expressed in multiple types of cancer; thus the MAGE-A1(96-104) and MAGE-A10(254-262) peptides may be considered for inclusion in vaccines against cancers of other histologic types, in addition to melanoma.
433 15781661 Administration of IFN-alpha enhances the efficacy of a granulocyte macrophage colony stimulating factor-secreting tumor cell vaccine.
434 15781661 The studies reported herein show that 50% of mice reject established B16 tumors following treatment with the combination of a granulocyte macrophage colony-stimulating factor-secreting tumor cell vaccine (B16.GM) and subclinical doses of recombinant murine IFN-alpha delivered at the vaccine site.
435 15781661 Furthermore, a 30-fold increase in the frequency of melanoma-associated antigen (Trp-2 and gp100) specific T cells was observed in mice treated with the combination when compared with unvaccinated controls.
436 15781661 These data show that IFN-alpha combined with a granulocyte macrophage colony-stimulating factor-secreting tumor cell vaccine significantly enhances vaccine potency and may represent a potential new approach for tumor immunotherapy.
437 15869409 Induction of antigen-specific immune responses against malignant brain tumors by intramuscular injection of sindbis DNA encoding gp100 and IL-18.
438 15869409 We investigated whether immunizing mice with xenogeneic DNA encoding human gp100 and mouse IL-18 would enhance the antitumor responses.
439 15869409 Genetic immunization using plasmid pSin 9001 DNA codelivery of human gp100 and mouse IL-18 resulted in enhanced protective and therapeutic effects on the malignant brain tumors.
440 15869409 The antitumor and protective effects were mediated by both CD4(+)/CD8(+) T cells and IFN-gamma.
441 15869409 Immunogene therapy with the improved Sindbis virus vector expressing xenogeneic gp100 and syngeneic IL-18 may be an excellent approach for developing a new treatment protocol.
442 15869409 Induction of antigen-specific immune responses against malignant brain tumors by intramuscular injection of sindbis DNA encoding gp100 and IL-18.
443 15869409 We investigated whether immunizing mice with xenogeneic DNA encoding human gp100 and mouse IL-18 would enhance the antitumor responses.
444 15869409 Genetic immunization using plasmid pSin 9001 DNA codelivery of human gp100 and mouse IL-18 resulted in enhanced protective and therapeutic effects on the malignant brain tumors.
445 15869409 The antitumor and protective effects were mediated by both CD4(+)/CD8(+) T cells and IFN-gamma.
446 15869409 Immunogene therapy with the improved Sindbis virus vector expressing xenogeneic gp100 and syngeneic IL-18 may be an excellent approach for developing a new treatment protocol.
447 15869409 Induction of antigen-specific immune responses against malignant brain tumors by intramuscular injection of sindbis DNA encoding gp100 and IL-18.
448 15869409 We investigated whether immunizing mice with xenogeneic DNA encoding human gp100 and mouse IL-18 would enhance the antitumor responses.
449 15869409 Genetic immunization using plasmid pSin 9001 DNA codelivery of human gp100 and mouse IL-18 resulted in enhanced protective and therapeutic effects on the malignant brain tumors.
450 15869409 The antitumor and protective effects were mediated by both CD4(+)/CD8(+) T cells and IFN-gamma.
451 15869409 Immunogene therapy with the improved Sindbis virus vector expressing xenogeneic gp100 and syngeneic IL-18 may be an excellent approach for developing a new treatment protocol.
452 15869409 Induction of antigen-specific immune responses against malignant brain tumors by intramuscular injection of sindbis DNA encoding gp100 and IL-18.
453 15869409 We investigated whether immunizing mice with xenogeneic DNA encoding human gp100 and mouse IL-18 would enhance the antitumor responses.
454 15869409 Genetic immunization using plasmid pSin 9001 DNA codelivery of human gp100 and mouse IL-18 resulted in enhanced protective and therapeutic effects on the malignant brain tumors.
455 15869409 The antitumor and protective effects were mediated by both CD4(+)/CD8(+) T cells and IFN-gamma.
456 15869409 Immunogene therapy with the improved Sindbis virus vector expressing xenogeneic gp100 and syngeneic IL-18 may be an excellent approach for developing a new treatment protocol.
457 16000953 A homologous series of Ii-Key/gp100(46-58) hybrids was synthesized to test the influence of spacer length (between Ii-Key and the gp100(48-58) epitope) on in vivo enhancement of gp100(48-58)-specific CD4+ T-lymphocyte responses.
458 16000953 As measured by IFN-gamma and IL-4 ELISPOT cytokine assays, the most effective vaccine hybrid was the one with a shorter linker between Ii-Key and the epitope.
459 16061687 To exploit these properties for immunization purposes, we conjugated the melanoma antigen tyrosinase-related protein (TRP)-2 to alphaDEC-205 antibodies and immunized mice with these conjugates together with dendritic cell-activating oligonucleotides (CpG).
460 16061687 Approximately 70% of the animals were cured from existing tumors by treatment with alphaDEC conjugates carrying two different melanoma antigens (TRP-2 and gp100).
461 16061687 This protection was due to induction of melanoma-specific CD4 and CD8 responses.
462 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.
463 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).
464 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.
465 16157421 We have shown that FITC-labeled nLT is taken up by human dendritic cells (hDC) in vitro and in mouse skin, and induces maturation and activation of hDC in vitro. hDC matured with nLT enhanced nonspecific melanoma antigen uptake and presentation to autologous CD8+ T cells.
466 16157421 In mouse in vivo studies, nLT or LTB were applied on the skin either mixed with recombinant gp100 or genetically fused with a multiepitope polypeptide (MEP).
467 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.
468 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).
469 16424050 We sought to measure the relative growth rates of T cells and tumor cells in a model using transgenic CD8(+) T cells specific for the gp100(25-33) H-2D(b) epitope (called pmel-1) to treat large, well-established s.c.
470 16567969 The melanoma differentiation antigens gp100, MART-1 and tyrosinase are involved in a common pathway of melanin synthesis.
471 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).
472 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.
473 16567969 The melanoma differentiation antigens gp100, MART-1 and tyrosinase are involved in a common pathway of melanin synthesis.
474 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).
475 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.
476 16640539 The effects of gp100 and tyrosinase peptide vaccinations on nevi in melanoma patients.
477 16651447 We sought to improve on this strategy by combining xenogeneic DNA vaccination with an agonist anti-glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) monoclonal antibody (mAb), DTA-1, which has been shown previously both to costimulate activated effector CD4(+) and CD8(+) T cells and to inhibit the suppressive activity of CD4(+)CD25(+) regulatory T cells.
478 16651447 We found that ligation of GITR with DTA-1 just before the second, but not the first, of 3 weekly DNA immunizations enhanced primary CD8(+) T-cell responses against the melanoma differentiation antigens gp100 and tyrosinase-related protein 2/dopachrome tautomerase and increased protection from a lethal challenge with B16 melanoma.
479 16651447 Finally, this effect on vaccine-induced CD8(+) T-cell responses was partially independent of CD4(+) T cells (both helper and regulatory), consistent with a direct costimulatory effect on the effector CD8(+) cells themselves.
480 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.
481 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.
482 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.
483 16651452 In all patients, treatment augmented significantly the percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell fraction.
484 16651452 An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed.
485 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.
486 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.
487 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.
488 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.
489 16651452 In all patients, treatment augmented significantly the percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell fraction.
490 16651452 An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed.
491 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.
492 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.
493 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.
494 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.
495 16651452 In all patients, treatment augmented significantly the percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell fraction.
496 16651452 An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed.
497 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.
498 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.
499 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.
500 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.
501 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.
502 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).
503 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.
504 16942445 Analysis of antitumor activity elicited by vaccination with combinations of interleukin-12 DNA with gp100 DNA or the chemokine CCL21 in vivo.
505 16942445 The antitumor efficacy of human melanoma-associated antigen (hgp100) and chemokine CCL21 in combination with interleukin-12 (IL-12) was evaluated in a syngeneic melanoma mouse model.
506 16942445 Coapplication of IL- 12 DNA with CCL21-encoding DNA (CCL21 DNA) or recombinant CCL21 (recCCL21) protein also showed some efficacy.
507 16942445 Triple therapy with IL-12 DNA, hgp100 DNA, and CCL21 DNA, however, showed less effect on tumor growth than double therapy with IL-12 DNA and hgp100 DNA.
508 16942445 These findings open a new route of investigation of IL-12 and gp100 or other tumor-associated antigens in the immunotherapy of a variety of tumors.
509 16942445 Analysis of antitumor activity elicited by vaccination with combinations of interleukin-12 DNA with gp100 DNA or the chemokine CCL21 in vivo.
510 16942445 The antitumor efficacy of human melanoma-associated antigen (hgp100) and chemokine CCL21 in combination with interleukin-12 (IL-12) was evaluated in a syngeneic melanoma mouse model.
511 16942445 Coapplication of IL- 12 DNA with CCL21-encoding DNA (CCL21 DNA) or recombinant CCL21 (recCCL21) protein also showed some efficacy.
512 16942445 Triple therapy with IL-12 DNA, hgp100 DNA, and CCL21 DNA, however, showed less effect on tumor growth than double therapy with IL-12 DNA and hgp100 DNA.
513 16942445 These findings open a new route of investigation of IL-12 and gp100 or other tumor-associated antigens in the immunotherapy of a variety of tumors.
514 16972742 The cervicovaginal citology is still the most accurate diagnosis method to detect SIL or CIN and invasive cancer in early stages, it is discussed the periodicity and group of women to whom the method must point.
515 17121795 In this study, we have established that a vaccine platform based on the coat protein of papaya mosaic virus (PapMV CP), previously shown to induce a humoral response, can induce major histocompatibility complex (MHC) class I cross-presentation of HLA-A*0201 epitopes from gp100, a melanoma antigen, and from influenza virus M1 matrix protein.
516 17121795 When we pulsed HLA-A*0201+ antigen-presenting cells (APCs) with the recombinant PapMV FLU or gp100, we noted that antigen-specific CD8+ T cells were highly reactive to these APCs, demonstrating that the epitope from the VLPs were processed and loaded on the MHC class I complex.
517 17255276 A phase I study of immunization using particle-mediated epidermal delivery of genes for gp100 and GM-CSF into uninvolved skin of melanoma patients.
518 17713000 The array of promiscuously expressed self-antigens was random and included well-known targets for cancer immunotherapy, such as alpha-fetoprotein, P1A, tyrosinase, and gp100.
519 17957800 A high-mannose form of gp100, as protein or as tumor lysate, not only interacted specifically with DC through DC-SIGN but also resulted in an enhanced antigen presentation to gp100-specific CD4(+) T cells.
520 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).
521 18317358 This vaccine was designed to activate MART-1-specific CD+8 and CD4+ T cells.
522 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.
523 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.
524 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.
525 18317358 Responses in CD8+ and CD4+ T cells to additional antigens were noted in 2 patients.
526 18392619 Tetramer analysis showed that vaccine-induced T cells recognizing gp100 and tyrosinase are present at the vitiligo lesions.
527 18392619 These T cells secrete IFN-gamma and IL-2 upon peptide specific stimulation as well as upon recognition of the autologous tumor.
528 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.
529 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.
530 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.
531 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.
532 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.
533 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.
534 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.
535 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.
536 18797450 Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances immune responses by inducing proliferation, maturation, and migration of dendritic cells (DCs) as well as expansion and differentiation of B and T lymphocytes.
537 18797450 We conducted a phase I/II trial of human GM-CSF DNA in conjunction with a multipeptide vaccine (gp100 and tyrosinase) in stage III/IV melanoma patients.
538 18797450 Eight patients (42%) developed CD8+ T-cell responses, defined by a > or =3 SD increase in baseline reactivity to tyrosinase or gp100 peptide in tetramer or intracellular cytokine staining (ICS) assays.
539 18797450 Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances immune responses by inducing proliferation, maturation, and migration of dendritic cells (DCs) as well as expansion and differentiation of B and T lymphocytes.
540 18797450 We conducted a phase I/II trial of human GM-CSF DNA in conjunction with a multipeptide vaccine (gp100 and tyrosinase) in stage III/IV melanoma patients.
541 18797450 Eight patients (42%) developed CD8+ T-cell responses, defined by a > or =3 SD increase in baseline reactivity to tyrosinase or gp100 peptide in tetramer or intracellular cytokine staining (ICS) assays.
542 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.
543 19047169 Improved tumor immunity using anti-tyrosinase related protein-1 monoclonal antibody combined with DNA vaccines in murine melanoma.
544 19047169 Passive immunization with monoclonal antibody TA99 targeting melanoma differentiation antigen tyrosinase-related protein-1 (Tyrp1; gp75) and active immunization with plasmid DNA encoding altered Tyrp1 both mediate tumor immunity in the B16 murine melanoma model.
545 19047169 TA99 is shown to increase induction of anti-Tyrp1 CD8+T-cell responses to DNA vaccination against Tyrp1 as assessed by IFN-gamma ELISPOT assays.
546 19047169 Furthermore, TA99 enhances DNA vaccination against a distinct melanoma antigen, gp100(pmel17/silver locus), improving antitumor efficacy, augmenting systemic CD8+ T-cell responses to gp100, and increasing CD8+ T-cell infiltration at the tumor site.
547 19047169 Epitope spreading was observed, with CD8+ T-cell responses generated to Tyrp1 peptide in mice receiving gp100 DNA vaccination in the presence of TA99.
548 19047169 In conclusion, TA99 enhances DNA vaccination against both the target antigen Tyrp1 and a distinct melanoma antigen gp100 in an Fc receptor-dependent mechanism, consistent with enhanced cross-presentation of tumor-derived antigen.
549 19047169 Improved tumor immunity using anti-tyrosinase related protein-1 monoclonal antibody combined with DNA vaccines in murine melanoma.
550 19047169 Passive immunization with monoclonal antibody TA99 targeting melanoma differentiation antigen tyrosinase-related protein-1 (Tyrp1; gp75) and active immunization with plasmid DNA encoding altered Tyrp1 both mediate tumor immunity in the B16 murine melanoma model.
551 19047169 TA99 is shown to increase induction of anti-Tyrp1 CD8+T-cell responses to DNA vaccination against Tyrp1 as assessed by IFN-gamma ELISPOT assays.
552 19047169 Furthermore, TA99 enhances DNA vaccination against a distinct melanoma antigen, gp100(pmel17/silver locus), improving antitumor efficacy, augmenting systemic CD8+ T-cell responses to gp100, and increasing CD8+ T-cell infiltration at the tumor site.
553 19047169 Epitope spreading was observed, with CD8+ T-cell responses generated to Tyrp1 peptide in mice receiving gp100 DNA vaccination in the presence of TA99.
554 19047169 In conclusion, TA99 enhances DNA vaccination against both the target antigen Tyrp1 and a distinct melanoma antigen gp100 in an Fc receptor-dependent mechanism, consistent with enhanced cross-presentation of tumor-derived antigen.
555 19047169 Improved tumor immunity using anti-tyrosinase related protein-1 monoclonal antibody combined with DNA vaccines in murine melanoma.
556 19047169 Passive immunization with monoclonal antibody TA99 targeting melanoma differentiation antigen tyrosinase-related protein-1 (Tyrp1; gp75) and active immunization with plasmid DNA encoding altered Tyrp1 both mediate tumor immunity in the B16 murine melanoma model.
557 19047169 TA99 is shown to increase induction of anti-Tyrp1 CD8+T-cell responses to DNA vaccination against Tyrp1 as assessed by IFN-gamma ELISPOT assays.
558 19047169 Furthermore, TA99 enhances DNA vaccination against a distinct melanoma antigen, gp100(pmel17/silver locus), improving antitumor efficacy, augmenting systemic CD8+ T-cell responses to gp100, and increasing CD8+ T-cell infiltration at the tumor site.
559 19047169 Epitope spreading was observed, with CD8+ T-cell responses generated to Tyrp1 peptide in mice receiving gp100 DNA vaccination in the presence of TA99.
560 19047169 In conclusion, TA99 enhances DNA vaccination against both the target antigen Tyrp1 and a distinct melanoma antigen gp100 in an Fc receptor-dependent mechanism, consistent with enhanced cross-presentation of tumor-derived antigen.
561 19242378 On the basis of previously established methods to generate DC from mouse embryonic stem cells (ES-DC), 4 kinds of genetically modified ES-DC, which expressed the melanoma-associated antigens, glypican-3, secreted protein acidic and rich in cysteine, tyrosinase-related protein-2, or gp100 were generated.
562 19276379 CTL activation using the natural low-affinity epitope 222-229 from tyrosinase-related protein 1 leads to tumor rejection.
563 19276379 We have examined the peptide specificity of a strongly protective T-cell response that eradicates established B16 melanoma and find that the recognized epitope is generated by a low-affinity MHC class I ligand from tyrosinase-related protein 1 (TRP1).
564 19276379 The key finding in this study is that protection from freshly implanted or established B16 tumors is primarily mediated by TRP1(222)-specific CTL and not by CTL specific for more traditional melanoma antigens such as TRP2 or gp100.
565 19318559 DC were electroporated with mRNA encoding gp100 or tyrosinase, labeled with indium-111 and superparamagnetic iron oxide particles, and injected intranodally in melanoma patients 24 to 48 hours before scheduled dissection of regional lymph nodes.
566 19494262 IFN-alpha enhances peptide vaccine-induced CD8+ T cell numbers, effector function, and antitumor activity.
567 19494262 Type I IFNs, including IFN-alpha, enhance Ag presentation and promote the expansion, survival, and effector function of CD8(+) CTL during viral infection.
568 19494262 IFN-alpha dramatically increased the accumulation of gp100-specific, IFN-gamma-secreting, CD8(+) T cells in the tumor through reduced apoptosis and enhanced proliferation of Ag-specific CD8(+) T cells.
569 19494262 IFN-alpha treatment also greatly increased the long-term maintenance of pmel-1 CD8(+) T cells with an effector memory phenotype, a process that required expression of IFN-alpha receptor on the T cells and IL-15 in the host.
570 19496531 Five patients developed CD8+ cells binding gp100(280-288) HLA-A2-restricted tetramer.
571 19496531 One patient had an increase in CD8+ IFN-gamma+ cells.
572 19609242 We injected intradermally protamine-stabilized mRNAs coding for Melan-A, Tyrosinase, gp100, Mage-A1, Mage-A3, and Survivin in 21 metastatic melanoma patients.
573 19609242 Granulocyte macrophage colony-stimulating factor was applied as an adjuvant.
574 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.
575 19626052 Transgenic expression of human gp100 and RANTES at specific time points for suppression of melanoma.
576 19626052 For gene-based vaccination against B16 melanoma in C57BL/6JNarl mice, initial priming with mouse RANTES cDNA followed 24 h later by human gp100 DNA vaccination, and later boosting with a viral vector expressing mRANTES and hgp100 strongly suppressed B16/hgp100 primary tumors and lung metastasis.
577 19626052 B16/hgp100 melanoma cells were resistant to the ligands TRAIL and FasL in vitro but sensitized to them in vivo owing to the priming effect of cytokines in response to vaccination.
578 19626052 Transgenic expression of human gp100 and RANTES at specific time points for suppression of melanoma.
579 19626052 For gene-based vaccination against B16 melanoma in C57BL/6JNarl mice, initial priming with mouse RANTES cDNA followed 24 h later by human gp100 DNA vaccination, and later boosting with a viral vector expressing mRANTES and hgp100 strongly suppressed B16/hgp100 primary tumors and lung metastasis.
580 19626052 B16/hgp100 melanoma cells were resistant to the ligands TRAIL and FasL in vitro but sensitized to them in vivo owing to the priming effect of cytokines in response to vaccination.
581 19787240 By using electroporation-mediated gene/pDNA delivery, the anti-tumor efficacy of vaccination with pDNAs encoding gp100, TRP2 and Ii-PADRE was facilitated by administration of soluble form of EphB4 fused with human serum albumin (sEphB4-HSA), or by co-delivery of pDNAs encoding Angiostatin and/or Endostatin.
582 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.
583 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.
584 20370546 Patients bearing metastatic melanoma were successfully treated with ACT using peripheral blood lymphocytes transduced with Mart-1 and gp100 tumor-associated epitopes.
585 20439916 Our previous studies have demonstrated that the natural chaperone complexes of full-length tumor protein Ags (e.g., gp100) and large stress proteins (e.g., hsp110 and grp170) with exceptional Ag-holding capabilities augment potent tumor protective immunity.
586 20439916 Immunization with hsp110- or grp170-tyrosinase-related protein 2 (TRP2(175-192)) peptide complexes effectively primed CD8(+) T cells reactive with TRP2-derived, MHC class I-restricted epitope.
587 20439916 Furthermore, immunization with combined chaperone vaccines directed against two melanoma protein Ags (i.e., gp100 and TRP2) significantly improved overall anti-tumor efficacy when compared with either of the single Ag vaccine.
588 20439916 Our previous studies have demonstrated that the natural chaperone complexes of full-length tumor protein Ags (e.g., gp100) and large stress proteins (e.g., hsp110 and grp170) with exceptional Ag-holding capabilities augment potent tumor protective immunity.
589 20439916 Immunization with hsp110- or grp170-tyrosinase-related protein 2 (TRP2(175-192)) peptide complexes effectively primed CD8(+) T cells reactive with TRP2-derived, MHC class I-restricted epitope.
590 20439916 Furthermore, immunization with combined chaperone vaccines directed against two melanoma protein Ags (i.e., gp100 and TRP2) significantly improved overall anti-tumor efficacy when compared with either of the single Ag vaccine.
591 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.
592 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.
593 21182075 Three spliced peptides, derived from FGF-5, melanoma protein gp100 and nuclear protein SP110, have been described.
594 21182075 The FGF-5 and gp100 peptides are more efficiently produced by the standard proteasome, whereas the SP110 peptide is more efficiently produced by the immunoproteasome.
595 21182075 Three spliced peptides, derived from FGF-5, melanoma protein gp100 and nuclear protein SP110, have been described.
596 21182075 The FGF-5 and gp100 peptides are more efficiently produced by the standard proteasome, whereas the SP110 peptide is more efficiently produced by the immunoproteasome.
597 21250746 Following immunization using US exposure and Man-PEG(2000) bubble lipoplexes constructed with pUb-M, which expresses ubiquitylated melanoma-specific antigens (gp100 and TRP-2), the secretion of Th1 cytokines (IFN-γ and TNF-α) and the activities of cytotoxic T lymphocytes (CTLs) were specifically enhanced in the presence of B16BL6 melanoma antigens.
598 21327126 Using an inducible and rapid expression plasmid, vaccination with several antigens of different length and epitope composition, including TRp-2, gp100 and MUC18, was evaluated against glioma tumor cells.
599 21327126 Characteristics that consistently improved anti-tumor immunity include: long peptides with immunodominant and cryptic CD8(+) epitopes, and strong CD4(+) Th epitopes.
600 21372855 We assessed the level of anti-tumor immunity conferred by this engineered lentivector encoding the melanoma antigen gp100 in a mouse model.
601 21372855 A single prime vaccination of the engineered lentivectors can elicit a high frequency (up to 10%) of gp100-specific CD8(+) T cells in peripheral blood 3 weeks after the vaccination and this response will be maintained at around 5% for up to 8 weeks.
602 21372855 We assessed the level of anti-tumor immunity conferred by this engineered lentivector encoding the melanoma antigen gp100 in a mouse model.
603 21372855 A single prime vaccination of the engineered lentivectors can elicit a high frequency (up to 10%) of gp100-specific CD8(+) T cells in peripheral blood 3 weeks after the vaccination and this response will be maintained at around 5% for up to 8 weeks.
604 21374333 Here we describe the construction of a DNA vaccine against malignant melanomas using: (i) the tumor-associated antigen gp100 (or pmel17), known to be over-expressed in many malignant melanomas (3,4), and (ii) the granulocyte macrophage stimulating factor (GM-CSF) which has been shown to have a stimulatory effect on humoral and cellular immune responses (5).
605 21577140 The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC).
606 21577140 This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containing autologous TriMix-DC co-electroporated with mRNA encoding a human leukocyte antigen class II-targeting signal linked to 1 of 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, and gp100) in patients with advanced melanoma.
607 21746967 We found that lv-expressing xenogenic human gp100 could induce potent CD8 responses that cross-react with mouse gp100.
608 21746967 Although CD8 response plays a dominant role after lv immunization, both CD4 and CD8 T cells are responsible for the immune prevention.
609 21746967 In addition, we surprisingly found that CD4 help was not only critical for generating primary CD8 responses, but also important for secondary CD8 responses of vv boost.
610 21746967 CD4 depletion prior to lv prime or prior to vv boost substantially reduced the magnitude of secondary CD8 effector and memory responses, and severely compromised the effect of cancer immune prevention.
611 21940815 It has been observed that LAM cells express markers associated with melanocytic differentiation, including gp100 and MART-1.
612 21993558 MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
613 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.
614 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.
615 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.
616 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.
617 21993558 MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
618 21993558 Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
619 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.
620 21993558 MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
621 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.
622 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.
623 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.
624 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.
625 21993558 MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
626 21993558 Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
627 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.
628 21993558 MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
629 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.
630 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.
631 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.
632 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.
633 21993558 MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
634 21993558 Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
635 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.
636 21993558 MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
637 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.
638 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.
639 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.
640 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.
641 21993558 MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
642 21993558 Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
643 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.
644 21993558 MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
645 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.
646 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.
647 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.
648 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.
649 21993558 MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
650 21993558 Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
651 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.
652 21993558 MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
653 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.
654 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.
655 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.
656 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.
657 21993558 MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
658 21993558 Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
659 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.
660 21993558 MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
661 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.
662 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.
663 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.
664 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.
665 21993558 MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
666 21993558 Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
667 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.
668 21993558 MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro.
669 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.
670 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.
671 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.
672 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.
673 21993558 MART-1, gp100, tyrosinase, and CD271 expression were studied in MEL-XY1 and MEL-XY3 colonies.
674 21993558 Finally, clonogenic, MART-1/gp100-expressing cells were lysed by specific CD8 lymphocytes.
675 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.
676 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.
677 22021080 Multiparameter flow cytometry was used to measure the frequency of CD8(+) T cells specific for gp100, MART-1, tyrosinase and influenza (FLU) peptides.
678 22021080 Expression of CD45RA/CCR7 on CD8(+) tet(+) T cells and CD25, CD27, CD28 on all circulating T cells was determined.
679 22021080 Only gp100- and MART-1-specific T cells differentiated to CD45RA(+) CCR7(-) effector/memory T cells.
680 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.
681 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.
682 22021080 Multiparameter flow cytometry was used to measure the frequency of CD8(+) T cells specific for gp100, MART-1, tyrosinase and influenza (FLU) peptides.
683 22021080 Expression of CD45RA/CCR7 on CD8(+) tet(+) T cells and CD25, CD27, CD28 on all circulating T cells was determined.
684 22021080 Only gp100- and MART-1-specific T cells differentiated to CD45RA(+) CCR7(-) effector/memory T cells.
685 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.
686 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.
687 22021080 Multiparameter flow cytometry was used to measure the frequency of CD8(+) T cells specific for gp100, MART-1, tyrosinase and influenza (FLU) peptides.
688 22021080 Expression of CD45RA/CCR7 on CD8(+) tet(+) T cells and CD25, CD27, CD28 on all circulating T cells was determined.
689 22021080 Only gp100- and MART-1-specific T cells differentiated to CD45RA(+) CCR7(-) effector/memory T cells.
690 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.
691 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.
692 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.
693 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.
694 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.
695 22895835 Based on immunohistochemical analysis, CD8 and IL-17 were not involved in the prognosis.
696 23087058 To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC class I and II (MHC-I/II)-restricted epitopes.
697 23087058 Patients received intranodal vaccinations with cytokine-matured DCs loaded with keyhole limpet hemocyanin and MHC-I alone or MHC-I/II-restricted tumor-associated antigens (TAA) of tyrosinase and gp100, depending on their HLA-DR4 status.
698 23087058 In 4 of 15 patients vaccinated with MHC-I/II-loaded DCs and 1 of 14 patients vaccinated with MHC-I-loaded DCs, we detected TAA-specific CD8(+) T cells with maintained IFN-γ production in skin test infiltrating lymphocyte (SKIL) cultures and circulating TAA-specific CD8(+) T cells.
699 23087058 If TAA-specific CD4(+) T-cell responses were detected in SKIL cultures, it coincided with TAA-specific CD8(+) T-cell responses.
700 23087058 In 3 of 13 patients tested, we detected TAA-specific CD4(+)CD25(+)FoxP3(-) T cells with high proliferative capacity and IFN-γ production, indicating that these were not regulatory T cells.
701 23087058 In conclusion, coactivating TAA-specific CD4(+) T-helper cells with DCs pulsed with both MHC class I and II-restricted epitopes augments TAA-specific CD8(+) T-cell responses, contributing to improved clinical responses.
702 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.
703 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.
704 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).
705 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.
706 23333935 In situ Ad.Flagrp170 therapy provokes systemic activation of CTLs that recognize several antigens naturally expressing in melanoma (e.g., gp100/PMEL and TRP2/DCT).
707 23333935 Antibody neutralization assays show that IL-12 and IFN-γ are essential for the Flagrp170-elicited antitumor response, which also involves CD8(+) T cells and natural killer cells.
708 23603858 Murine responses to recombinant MVA versus ALVAC vaccines against tumor-associated antigens, gp100 and 5T4.
709 23603858 Here, we compared 2 replication-deficient poxviruses modified vaccinia Ankara (MVA) and ALVAC(2) in their ability to induce antigen expression and immunogenicity of the tumor-associated antigens (TAAs) 5T4 and gp100.
710 23603858 Murine responses to recombinant MVA versus ALVAC vaccines against tumor-associated antigens, gp100 and 5T4.
711 23603858 Here, we compared 2 replication-deficient poxviruses modified vaccinia Ankara (MVA) and ALVAC(2) in their ability to induce antigen expression and immunogenicity of the tumor-associated antigens (TAAs) 5T4 and gp100.
712 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.
713 24108701 Altered peptide ligands (APLs) were designed to enhance MHC binding and hence T cell recognition of gp100 in HLA-DR4(+) melanoma patients.
714 24108701 Nevertheless, heterogeneous preferences of CD4(+) T cells from several HLA-DR4(+) melanoma patients for different gp100 APLs suggested highly variable TCR usage, even among six patients who had been vaccinated against the wild-type gp100 peptide.
715 24108701 Altered peptide ligands (APLs) were designed to enhance MHC binding and hence T cell recognition of gp100 in HLA-DR4(+) melanoma patients.
716 24108701 Nevertheless, heterogeneous preferences of CD4(+) T cells from several HLA-DR4(+) melanoma patients for different gp100 APLs suggested highly variable TCR usage, even among six patients who had been vaccinated against the wild-type gp100 peptide.
717 24713579 Artificial antigen-presenting cells expressing CD80, CD70, and 4-1BB ligand efficiently expand functional T cells specific to tumor-associated antigens.
718 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).
719 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.
720 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.
721 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.
722 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.
723 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.
724 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.
725 24756419 The 6MHP vaccine induces both CD4(+) and CD8(+) T cell responses against melanoma antigens.
726 25205103 The nucleosome-binding protein HMGN1 is a potent alarmin that binds TLR4 and induces antigen-specific Th1 immune responses, but its contributions to antitumor immunity have not been explored.
727 25205103 Moreover, mice vaccinated with a DNA vector expressing an HMGN1-gp100 fusion protein manifested gp100-specific, Th1-polarized immune responses, acquiring resistance to challenge with mouse B16F1 melanoma.
728 26241951 A multi-trimeric fusion of CD40L and gp100 tumor antigen activates dendritic cells and enhances survival in a B16-F10 melanoma DNA vaccine model.
729 26241951 The spontaneously-multimerizing gene Surfactant Protein D (SPD) was used to fuse gp100 tumor antigen and CD40L, creating the recombinant protein SPD-gp100-CD40L.
730 26241951 DNA vaccination with SPD-gp100-CD40L plasmid, together with plasmids encoding IL-12p70 and GM-CSF, significantly enhanced survival and inhibited tumor growth in a B16-F10 melanoma model.
731 26241951 These data support a model where DNA vaccination with SPD-gp100-CD40L targets gp100 to DC in situ, induces activation of these DC, and generates a protective anti-tumor response when given in combination with IL-12p70 and GM-CSF plasmids.
732 26241951 A multi-trimeric fusion of CD40L and gp100 tumor antigen activates dendritic cells and enhances survival in a B16-F10 melanoma DNA vaccine model.
733 26241951 The spontaneously-multimerizing gene Surfactant Protein D (SPD) was used to fuse gp100 tumor antigen and CD40L, creating the recombinant protein SPD-gp100-CD40L.
734 26241951 DNA vaccination with SPD-gp100-CD40L plasmid, together with plasmids encoding IL-12p70 and GM-CSF, significantly enhanced survival and inhibited tumor growth in a B16-F10 melanoma model.
735 26241951 These data support a model where DNA vaccination with SPD-gp100-CD40L targets gp100 to DC in situ, induces activation of these DC, and generates a protective anti-tumor response when given in combination with IL-12p70 and GM-CSF plasmids.
736 26405571 In an attempt to further improve the therapeutic responses, we treated 15 patients with melanoma, with autologous monocyte-derived immature DC electroporated with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively active TLR4 (caTLR4) together with mRNA encoding a tumor-associated antigen (TAA; respectively gp100 or tyrosinase).
737 26405571 In conclusion, autologous mRNA-optimized DC can be safely administered intranodally to patients with metastatic melanoma but showed limited immunological responses against tyrosinase and gp100.
738 26405571 In an attempt to further improve the therapeutic responses, we treated 15 patients with melanoma, with autologous monocyte-derived immature DC electroporated with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively active TLR4 (caTLR4) together with mRNA encoding a tumor-associated antigen (TAA; respectively gp100 or tyrosinase).
739 26405571 In conclusion, autologous mRNA-optimized DC can be safely administered intranodally to patients with metastatic melanoma but showed limited immunological responses against tyrosinase and gp100.