Ignet

Gene Information

Gene symbol: C8orf4

Gene name: chromosome 8 open reading frame 4

HGNC ID: 1357

Synonyms: TC-1, hTC-1

Related Genes

#	Gene Symbol	Number of hits
1	ADCY10	1 hits
2	B3GAT1	1 hits
3	BCL2L1	1 hits
4	BIRC5	1 hits
5	BTLA	1 hits
6	CALR	1 hits
7	CCL5	1 hits
8	CD27	1 hits
9	CD28	1 hits
10	CD4	1 hits
11	CD40	1 hits
12	CD40LG	1 hits
13	CD44	1 hits
14	CD8A	1 hits
15	CSF2	1 hits
16	CTLA4	1 hits
17	CXCL10	1 hits
18	CXCL9	1 hits
19	DARC	1 hits
20	EOMES	1 hits
21	FAS	1 hits
22	FCGR3A	1 hits
23	HLA-A	1 hits
24	HLA-B	1 hits
25	HSPA1A	1 hits
26	IFNG	1 hits
27	IL10	1 hits
28	IL10RA	1 hits
29	IL12A	1 hits
30	IL15	1 hits
31	IL17A	1 hits
32	IL2	1 hits
33	IL2RA	1 hits
34	IL4	1 hits
35	IL7	1 hits
36	KLRK1	1 hits
37	LAMP1	1 hits
38	NCAM1	1 hits
39	PDCD1	1 hits
40	PPBP	1 hits
41	SLC6A10P	1 hits
42	SOCS1	1 hits
43	SOX2	1 hits
44	STAT3	1 hits
45	TBX21	1 hits
46	TH1L	1 hits
47	TLR2	1 hits
48	TLR4	1 hits
49	TLR5	1 hits
50	TNF	1 hits
51	TNFRSF10B	1 hits
52	TNFRSF9	1 hits
53	TP53	1 hits
54	TSPAN7	1 hits
55	VEGFA	1 hits
56	VHLL	1 hits
57	VWS	1 hits

Related Sentences

#	PMID	Sentence
1	8548765	Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity.
2	8548765	In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1).
3	8548765	Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7.
4	8548765	All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection.
5	8548765	Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden.
6	8548765	Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity.
7	8548765	In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1).
8	8548765	Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7.
9	8548765	All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection.
10	8548765	Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden.
11	10510345	Several lines of evidence suggest that an IFN-gamma-producing, Th1/Tc1 phenotype may be optimal for tumor rejection.
12	10803024	Both CD4+ Th1 and CD8+ Tc1 lymphocytes are believed to mediate protection by producing of IFN-gamma, a pitoval cytokine that induces anti-Toxoplasma effector mechanisms in macrophages.
13	11313782	We previously found that recombinant vaccinia and naked DNA vaccines containing the chimeric Sig/E7/LAMP-1 gene were capable of controlling the growth of HPV-16 E7-expressing tumor cells (TC-1).
14	11313782	At a dose of 1 x 10(6) TC-1 cells per mouse, Sig/E7/LAMP-1 DNA provided 100% protection against subcutaneous growth of tumors, while Vac-Sig/E7/LAMP-1 protected only 40% of the mice.
15	11313782	Furthermore, Sig/E7/LAMP-1 DNA vaccines are capable of protecting against challenge with a more stringent subclone of TC-1 (TC-1 P2) established from TC-1 tumors that survived initial Sig/E7/LAMP-1 vaccinia vaccination.
16	11313782	Interestingly, Sig/E7/LAMP-1 vaccinia induced both E7-specific IFN-gamma- and IL4-secreting CD4(+) T cell precursors while Sig/E7/LAMP-1 DNA induced only E7-specific IFN-gamma-secreting CD4(+) T cell precursors.
17	11313782	We also found that IL-4 knockout C57BL/6 mice vaccinated with Sig/E7/LAMP-1 vaccinia exhibited a more potent antitumor effect than vaccinated wild-type C57BL/6 mice in our tumor protection experiments.
18	11313782	We previously found that recombinant vaccinia and naked DNA vaccines containing the chimeric Sig/E7/LAMP-1 gene were capable of controlling the growth of HPV-16 E7-expressing tumor cells (TC-1).
19	11313782	At a dose of 1 x 10(6) TC-1 cells per mouse, Sig/E7/LAMP-1 DNA provided 100% protection against subcutaneous growth of tumors, while Vac-Sig/E7/LAMP-1 protected only 40% of the mice.
20	11313782	Furthermore, Sig/E7/LAMP-1 DNA vaccines are capable of protecting against challenge with a more stringent subclone of TC-1 (TC-1 P2) established from TC-1 tumors that survived initial Sig/E7/LAMP-1 vaccinia vaccination.
21	11313782	Interestingly, Sig/E7/LAMP-1 vaccinia induced both E7-specific IFN-gamma- and IL4-secreting CD4(+) T cell precursors while Sig/E7/LAMP-1 DNA induced only E7-specific IFN-gamma-secreting CD4(+) T cell precursors.
22	11313782	We also found that IL-4 knockout C57BL/6 mice vaccinated with Sig/E7/LAMP-1 vaccinia exhibited a more potent antitumor effect than vaccinated wild-type C57BL/6 mice in our tumor protection experiments.
23	11313782	We previously found that recombinant vaccinia and naked DNA vaccines containing the chimeric Sig/E7/LAMP-1 gene were capable of controlling the growth of HPV-16 E7-expressing tumor cells (TC-1).
24	11313782	At a dose of 1 x 10(6) TC-1 cells per mouse, Sig/E7/LAMP-1 DNA provided 100% protection against subcutaneous growth of tumors, while Vac-Sig/E7/LAMP-1 protected only 40% of the mice.
25	11313782	Furthermore, Sig/E7/LAMP-1 DNA vaccines are capable of protecting against challenge with a more stringent subclone of TC-1 (TC-1 P2) established from TC-1 tumors that survived initial Sig/E7/LAMP-1 vaccinia vaccination.
26	11313782	Interestingly, Sig/E7/LAMP-1 vaccinia induced both E7-specific IFN-gamma- and IL4-secreting CD4(+) T cell precursors while Sig/E7/LAMP-1 DNA induced only E7-specific IFN-gamma-secreting CD4(+) T cell precursors.
27	11313782	We also found that IL-4 knockout C57BL/6 mice vaccinated with Sig/E7/LAMP-1 vaccinia exhibited a more potent antitumor effect than vaccinated wild-type C57BL/6 mice in our tumor protection experiments.
28	11714814	Depletion of the CD4+ T cell subset considerably reduces the ability of Lm-LLO-E7 to eliminate established TC-1 tumors.
29	11714814	Ab-mediated depletion of TGF-beta and CD25+ cells improves the effectiveness of Lm-E7 treatment, suggesting that TGF-beta and CD25+ cells are in part responsible for this suppressive response.
30	11714814	CD4+ T cells from mice immunized with Lm-E7 are capable of suppressing the ability of Lm-LLO-E7 to induce the regression of TC-1 when transferred to tumor-bearing mice.
31	11714814	Depletion of the CD4+ T cell subset considerably reduces the ability of Lm-LLO-E7 to eliminate established TC-1 tumors.
32	11714814	Ab-mediated depletion of TGF-beta and CD25+ cells improves the effectiveness of Lm-E7 treatment, suggesting that TGF-beta and CD25+ cells are in part responsible for this suppressive response.
33	11714814	CD4+ T cells from mice immunized with Lm-E7 are capable of suppressing the ability of Lm-LLO-E7 to induce the regression of TC-1 when transferred to tumor-bearing mice.
34	12193722	Multiple Chlamydia pneumoniae antigens prime CD8+ Tc1 responses that inhibit intracellular growth of this vacuolar pathogen.
35	12193722	Eighteen H-2(b) binding peptides representing sequences from 12 Cpn Ags sensitized target cells for MHC class I-restricted lysis by CD8(+) CTL generated from the spleens and lungs of infected mice.
36	12193722	Peptide-specific IFN-gamma-secreting CD8(+) T cells were present in local and systemic compartments after primary infection, and these cells expanded after pathogen re-exposure.
37	12193722	CD8(+) T cell lines to the 18 Cpn epitope-bearing peptides were cytotoxic, displayed a memory phenotype, and secreted IFN-gamma and TNF-alpha, but not IL-4.
38	12193722	Finally, Cpn peptide-specific CD8(+) CTL suppressed chlamydial growth in vitro by direct lysis of infected cells and by secretion of IFN-gamma and other soluble factors.
39	12547599	Moderately immunogenic HPV 16-associated tumours TC-1 (MHC class I(+), HPV 16 E6/E7(+), G12V Ha-ras(+)) and MK16/1/III ABC (MHC class I(-), HPV 16 E6/E7(+), G12V Ha-ras(+)), both of the H-2(b) haplotype and transplanted in syngeneic mice, were used to examine the adjuvant effects of IL-2 and dendritic cells for surgical therapy.
40	12579325	Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: Effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines.
41	12579325	The effectiveness of chemoimmunotherapy with ifosfamide derivative CBM-4A and recombinant IL-2, IL-12, GM-CSF, or genetically modified, cytokine-producing tumour vaccines was examined in mice carrying HPV16-associated, MHC class I+ (TC-1), and MHC class I- (MK16) tumours.
42	12579325	When the i.p. treatment of the MHC class I+ TC-1 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2, IL-12, or both cytokines, the growth of TC1 tumours was inhibited more vigorously than after the chemotherapy alone.
43	12579325	In contrast, when the i.p. treatment ofEthe MHC class I- MK16 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2 or IL-12, the cytokine therapy had no potentiating effect.
44	12579325	CBM-4A pretreatment was followed by peritumoral s.c. administration of IL-2 plus IL-12.
45	12579325	InEfurther experiments, the TC-1 and MK16 tumour-bearing mice were i.p. pretreated with CBM-4A and then injected s.c., peritumorally, with genetically modified, IL-2 or GM-CSF-producing MK16 tumour vaccines.
46	12579325	MK16 neoplasms, which were pretreated i.p. with CBM-4A, and then injected peritumorally with IL-2 or GM-CSF.
47	12579325	Peritumoral administration of GM-CSF had no antimetastatic effect, whereas peritumoral IL-2 administration produced substantial reduction of lung metastases.
48	12579325	Taken collectively, the results indicate that in mice carrying the MK16 (MHC class I-) tumour, the effects of the adjuvant cytokine therapy were substantially weaker than in mice carrying the TC-1 (MHC class I+) tumour inoculum.
49	12579325	Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: Effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines.
50	12579325	The effectiveness of chemoimmunotherapy with ifosfamide derivative CBM-4A and recombinant IL-2, IL-12, GM-CSF, or genetically modified, cytokine-producing tumour vaccines was examined in mice carrying HPV16-associated, MHC class I+ (TC-1), and MHC class I- (MK16) tumours.
51	12579325	When the i.p. treatment of the MHC class I+ TC-1 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2, IL-12, or both cytokines, the growth of TC1 tumours was inhibited more vigorously than after the chemotherapy alone.
52	12579325	In contrast, when the i.p. treatment ofEthe MHC class I- MK16 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2 or IL-12, the cytokine therapy had no potentiating effect.
53	12579325	CBM-4A pretreatment was followed by peritumoral s.c. administration of IL-2 plus IL-12.
54	12579325	InEfurther experiments, the TC-1 and MK16 tumour-bearing mice were i.p. pretreated with CBM-4A and then injected s.c., peritumorally, with genetically modified, IL-2 or GM-CSF-producing MK16 tumour vaccines.
55	12579325	MK16 neoplasms, which were pretreated i.p. with CBM-4A, and then injected peritumorally with IL-2 or GM-CSF.
56	12579325	Peritumoral administration of GM-CSF had no antimetastatic effect, whereas peritumoral IL-2 administration produced substantial reduction of lung metastases.
57	12579325	Taken collectively, the results indicate that in mice carrying the MK16 (MHC class I-) tumour, the effects of the adjuvant cytokine therapy were substantially weaker than in mice carrying the TC-1 (MHC class I+) tumour inoculum.
58	12579325	Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: Effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines.
59	12579325	The effectiveness of chemoimmunotherapy with ifosfamide derivative CBM-4A and recombinant IL-2, IL-12, GM-CSF, or genetically modified, cytokine-producing tumour vaccines was examined in mice carrying HPV16-associated, MHC class I+ (TC-1), and MHC class I- (MK16) tumours.
60	12579325	When the i.p. treatment of the MHC class I+ TC-1 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2, IL-12, or both cytokines, the growth of TC1 tumours was inhibited more vigorously than after the chemotherapy alone.
61	12579325	In contrast, when the i.p. treatment ofEthe MHC class I- MK16 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2 or IL-12, the cytokine therapy had no potentiating effect.
62	12579325	CBM-4A pretreatment was followed by peritumoral s.c. administration of IL-2 plus IL-12.
63	12579325	InEfurther experiments, the TC-1 and MK16 tumour-bearing mice were i.p. pretreated with CBM-4A and then injected s.c., peritumorally, with genetically modified, IL-2 or GM-CSF-producing MK16 tumour vaccines.
64	12579325	MK16 neoplasms, which were pretreated i.p. with CBM-4A, and then injected peritumorally with IL-2 or GM-CSF.
65	12579325	Peritumoral administration of GM-CSF had no antimetastatic effect, whereas peritumoral IL-2 administration produced substantial reduction of lung metastases.
66	12579325	Taken collectively, the results indicate that in mice carrying the MK16 (MHC class I-) tumour, the effects of the adjuvant cytokine therapy were substantially weaker than in mice carrying the TC-1 (MHC class I+) tumour inoculum.
67	12579325	Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: Effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines.
68	12579325	The effectiveness of chemoimmunotherapy with ifosfamide derivative CBM-4A and recombinant IL-2, IL-12, GM-CSF, or genetically modified, cytokine-producing tumour vaccines was examined in mice carrying HPV16-associated, MHC class I+ (TC-1), and MHC class I- (MK16) tumours.
69	12579325	When the i.p. treatment of the MHC class I+ TC-1 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2, IL-12, or both cytokines, the growth of TC1 tumours was inhibited more vigorously than after the chemotherapy alone.
70	12579325	In contrast, when the i.p. treatment ofEthe MHC class I- MK16 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2 or IL-12, the cytokine therapy had no potentiating effect.
71	12579325	CBM-4A pretreatment was followed by peritumoral s.c. administration of IL-2 plus IL-12.
72	12579325	InEfurther experiments, the TC-1 and MK16 tumour-bearing mice were i.p. pretreated with CBM-4A and then injected s.c., peritumorally, with genetically modified, IL-2 or GM-CSF-producing MK16 tumour vaccines.
73	12579325	MK16 neoplasms, which were pretreated i.p. with CBM-4A, and then injected peritumorally with IL-2 or GM-CSF.
74	12579325	Peritumoral administration of GM-CSF had no antimetastatic effect, whereas peritumoral IL-2 administration produced substantial reduction of lung metastases.
75	12579325	Taken collectively, the results indicate that in mice carrying the MK16 (MHC class I-) tumour, the effects of the adjuvant cytokine therapy were substantially weaker than in mice carrying the TC-1 (MHC class I+) tumour inoculum.
76	12615451	Monkeys immunized with HPV16L1 VLPs mounted a potent humoral response with strongly neutralizing antibodies and a strong L1-specific Th2 response as measured by IL-4 production by CD4+ T cells.
77	12615451	Monkeys immunized with plasmid DNA or an adenoviral vector expressing HPV16L1 showed strong Th1/Tc1 responses as measured by IFN-gamma production by CD4+ and/or CD8+ T cells and potent humoral responses, but only weakly neutralizing antibodies.
78	12750257	The linkage of gamma-tubulin to E7-targeted antigen to centrosomal compartments, resulted in enhanced MHC class I presentation of E7, and led to a marked increase in the number of E7-specific CD8(+) T-cell precursors as well as a potent CD4-independent antitumor effect against an E7-expressing tumor cell line, TC-1.
79	12750257	Our data suggest that the centrosome may be an important locus for MHC class I antigen processing and that targeting antigen to the centrosome can improve DNA vaccine potency.
80	12839960	Release of IL-12 was necessary to induce potent Tc(1) cells, because DCs from IL-12p40(-/-) mice, irrespective of their maturation level, generated low CTL responses, comparable with 48hDCs and 0hDCs from wild-type animals.
81	12883527	CD8+ T cells, NK cells and IFN-gamma are important for control of tumor with downregulated MHC class I expression by DNA vaccination.
82	12883527	We developed an E7-expressing murine tumor model with downregulated MHC class I expression, TC-1 P3 (A15).
83	12883527	We found that vaccination with DNA encoding E7 linked to Mycobacterial heat shock protein 70 (HSP70) generated a significant antitumor effect against TC-1 P3 (A15), while vaccination with E7/HSP70 vaccinia did not generate an appreciable antitumor effect.
84	12883527	Lymphocyte depletion experiments revealed that both CD8+ T cells and NK cells were essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
85	12883527	Furthermore, tumor protection experiments using IFN-gamma knockout mice revealed that IFN-gamma was essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
86	12883527	Our results demonstrate that vaccination with E7/HSP70 DNA results in a significant antitumor effect against a neoplasm with downregulated MHC class I expression and the importance of CD8+ T cells, NK cells, and IFN-gamma in generating this antitumor effect.
87	12883527	CD8+ T cells, NK cells and IFN-gamma are important for control of tumor with downregulated MHC class I expression by DNA vaccination.
88	12883527	We developed an E7-expressing murine tumor model with downregulated MHC class I expression, TC-1 P3 (A15).
89	12883527	We found that vaccination with DNA encoding E7 linked to Mycobacterial heat shock protein 70 (HSP70) generated a significant antitumor effect against TC-1 P3 (A15), while vaccination with E7/HSP70 vaccinia did not generate an appreciable antitumor effect.
90	12883527	Lymphocyte depletion experiments revealed that both CD8+ T cells and NK cells were essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
91	12883527	Furthermore, tumor protection experiments using IFN-gamma knockout mice revealed that IFN-gamma was essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
92	12883527	Our results demonstrate that vaccination with E7/HSP70 DNA results in a significant antitumor effect against a neoplasm with downregulated MHC class I expression and the importance of CD8+ T cells, NK cells, and IFN-gamma in generating this antitumor effect.
93	12883527	CD8+ T cells, NK cells and IFN-gamma are important for control of tumor with downregulated MHC class I expression by DNA vaccination.
94	12883527	We developed an E7-expressing murine tumor model with downregulated MHC class I expression, TC-1 P3 (A15).
95	12883527	We found that vaccination with DNA encoding E7 linked to Mycobacterial heat shock protein 70 (HSP70) generated a significant antitumor effect against TC-1 P3 (A15), while vaccination with E7/HSP70 vaccinia did not generate an appreciable antitumor effect.
96	12883527	Lymphocyte depletion experiments revealed that both CD8+ T cells and NK cells were essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
97	12883527	Furthermore, tumor protection experiments using IFN-gamma knockout mice revealed that IFN-gamma was essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
98	12883527	Our results demonstrate that vaccination with E7/HSP70 DNA results in a significant antitumor effect against a neoplasm with downregulated MHC class I expression and the importance of CD8+ T cells, NK cells, and IFN-gamma in generating this antitumor effect.
99	12883527	CD8+ T cells, NK cells and IFN-gamma are important for control of tumor with downregulated MHC class I expression by DNA vaccination.
100	12883527	We developed an E7-expressing murine tumor model with downregulated MHC class I expression, TC-1 P3 (A15).
101	12883527	We found that vaccination with DNA encoding E7 linked to Mycobacterial heat shock protein 70 (HSP70) generated a significant antitumor effect against TC-1 P3 (A15), while vaccination with E7/HSP70 vaccinia did not generate an appreciable antitumor effect.
102	12883527	Lymphocyte depletion experiments revealed that both CD8+ T cells and NK cells were essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
103	12883527	Furthermore, tumor protection experiments using IFN-gamma knockout mice revealed that IFN-gamma was essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
104	12883527	Our results demonstrate that vaccination with E7/HSP70 DNA results in a significant antitumor effect against a neoplasm with downregulated MHC class I expression and the importance of CD8+ T cells, NK cells, and IFN-gamma in generating this antitumor effect.
105	12922140	Vaccination with DNA encoding E7/HSP70 has generated a dramatic increase of E7-specific CD8+ T cell precursors and a strong antitumor effect against E7-expressing tumor (TC-1) in vaccinated mice.
106	12922140	Our results indicated that pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered via gene gun generated the highest number of E7-specific CD8+ T cells.
107	14645711	An adenoviral vector cancer vaccine that delivers a tumor-associated antigen/CD40-ligand fusion protein to dendritic cells.
108	14645711	This adenoviral vector encodes a fusion protein composed of an amino-terminal tumor-associated antigen fragment fused to the CD40 ligand (CD40L).
109	14645711	Subcutaneous injection of an adenoviral vector encoding a fusion protein of the human papillomavirus E7 foreign antigen linked to the CD40L generates CD8+ T cell-dependent immunoresistance to the growth of the E7-positive syngeneic TC-1 cancer cells in C57BL/6 mice for up to 1 year.
110	14645711	We also studied the s.c. injection of a vector carrying the gene for the human MUC-1 (hMUC-1) self-antigen fused to the CD40L.
111	14654953	Treatment of minimal residual disease after surgery or chemotherapy in mice carrying HPV16-associated tumours: Cytokine and gene therapy with IL-2 and GM-CSF.
112	14654953	Moderately immunogenic HPV16-associated tumours TC-1 (MHC class I+, HPV16 E6/E7+, G12V Ha-ras+) and MK16/1/IIIABC (MK16, MHC class I-, HPV16 E6/E7+, G12V Ha-ras+), both of the H-2b haplotype and transplanted in syngeneic mice, were used to examine the effects of local IL-2 and GM-CSF cytokine or gene therapy in the treatment of minimal residual tumour disease.
113	14654953	The mice carrying MHC class I+ TC-1 tumour residua after surgery were injected into the site of the surgery either with irradiated, IL-2 gene-modified MK16 tumour cells, or with recombinant IL-2.
114	14654953	Similarly, when the mice carrying TC-1 tumour residua after surgery were injected with recombinant GM-CSF, the recombinant GM-CSF inhibited growth of the tumour residua in the operated mice.
115	14654953	TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A and 8 days later, peritumourally, either with IL-2 gene-modified and IL-2-producing MK16 cells, or with recombinant IL-2.
116	14654953	TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A and then, peritumourally, either with irradiated, GM-CSF gene-modified and GM-CSF-producing MK16 cells, or with recombinant GM-CSF, it was found that both, the recombinant GM-CSF and GM-CSF gene therapy inhibited growth of tumour residua.
117	14654953	It has been found that both, recombinant IL-2 and GM-CSF, can inhibit growth of the tumour residua after surgery or chemotherapy.
118	14654953	The lung metastases in mice with surgical minimal residual tumour disease or in mice with tumour residua after chemotherapy were inhibited by IL-2 but not by GM-CSF.
119	14654953	In conclusion, the MHC class I+ and MHC class I-, HPV16-associated tumours were found to be sensitive to IL-2 and GM-CSF therapy after surgery or after cytoreductive chemotherapy.
120	14654953	Treatment of minimal residual disease after surgery or chemotherapy in mice carrying HPV16-associated tumours: Cytokine and gene therapy with IL-2 and GM-CSF.
121	14654953	Moderately immunogenic HPV16-associated tumours TC-1 (MHC class I+, HPV16 E6/E7+, G12V Ha-ras+) and MK16/1/IIIABC (MK16, MHC class I-, HPV16 E6/E7+, G12V Ha-ras+), both of the H-2b haplotype and transplanted in syngeneic mice, were used to examine the effects of local IL-2 and GM-CSF cytokine or gene therapy in the treatment of minimal residual tumour disease.
122	14654953	The mice carrying MHC class I+ TC-1 tumour residua after surgery were injected into the site of the surgery either with irradiated, IL-2 gene-modified MK16 tumour cells, or with recombinant IL-2.
123	14654953	Similarly, when the mice carrying TC-1 tumour residua after surgery were injected with recombinant GM-CSF, the recombinant GM-CSF inhibited growth of the tumour residua in the operated mice.
124	14654953	TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A and 8 days later, peritumourally, either with IL-2 gene-modified and IL-2-producing MK16 cells, or with recombinant IL-2.
125	14654953	TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A and then, peritumourally, either with irradiated, GM-CSF gene-modified and GM-CSF-producing MK16 cells, or with recombinant GM-CSF, it was found that both, the recombinant GM-CSF and GM-CSF gene therapy inhibited growth of tumour residua.
126	14654953	It has been found that both, recombinant IL-2 and GM-CSF, can inhibit growth of the tumour residua after surgery or chemotherapy.
127	14654953	The lung metastases in mice with surgical minimal residual tumour disease or in mice with tumour residua after chemotherapy were inhibited by IL-2 but not by GM-CSF.
128	14654953	In conclusion, the MHC class I+ and MHC class I-, HPV16-associated tumours were found to be sensitive to IL-2 and GM-CSF therapy after surgery or after cytoreductive chemotherapy.
129	14654953	Treatment of minimal residual disease after surgery or chemotherapy in mice carrying HPV16-associated tumours: Cytokine and gene therapy with IL-2 and GM-CSF.
130	14654953	Moderately immunogenic HPV16-associated tumours TC-1 (MHC class I+, HPV16 E6/E7+, G12V Ha-ras+) and MK16/1/IIIABC (MK16, MHC class I-, HPV16 E6/E7+, G12V Ha-ras+), both of the H-2b haplotype and transplanted in syngeneic mice, were used to examine the effects of local IL-2 and GM-CSF cytokine or gene therapy in the treatment of minimal residual tumour disease.
131	14654953	The mice carrying MHC class I+ TC-1 tumour residua after surgery were injected into the site of the surgery either with irradiated, IL-2 gene-modified MK16 tumour cells, or with recombinant IL-2.
132	14654953	Similarly, when the mice carrying TC-1 tumour residua after surgery were injected with recombinant GM-CSF, the recombinant GM-CSF inhibited growth of the tumour residua in the operated mice.
133	14654953	TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A and 8 days later, peritumourally, either with IL-2 gene-modified and IL-2-producing MK16 cells, or with recombinant IL-2.
134	14654953	TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A and then, peritumourally, either with irradiated, GM-CSF gene-modified and GM-CSF-producing MK16 cells, or with recombinant GM-CSF, it was found that both, the recombinant GM-CSF and GM-CSF gene therapy inhibited growth of tumour residua.
135	14654953	It has been found that both, recombinant IL-2 and GM-CSF, can inhibit growth of the tumour residua after surgery or chemotherapy.
136	14654953	The lung metastases in mice with surgical minimal residual tumour disease or in mice with tumour residua after chemotherapy were inhibited by IL-2 but not by GM-CSF.
137	14654953	In conclusion, the MHC class I+ and MHC class I-, HPV16-associated tumours were found to be sensitive to IL-2 and GM-CSF therapy after surgery or after cytoreductive chemotherapy.
138	14654953	Treatment of minimal residual disease after surgery or chemotherapy in mice carrying HPV16-associated tumours: Cytokine and gene therapy with IL-2 and GM-CSF.
139	14654953	Moderately immunogenic HPV16-associated tumours TC-1 (MHC class I+, HPV16 E6/E7+, G12V Ha-ras+) and MK16/1/IIIABC (MK16, MHC class I-, HPV16 E6/E7+, G12V Ha-ras+), both of the H-2b haplotype and transplanted in syngeneic mice, were used to examine the effects of local IL-2 and GM-CSF cytokine or gene therapy in the treatment of minimal residual tumour disease.
140	14654953	The mice carrying MHC class I+ TC-1 tumour residua after surgery were injected into the site of the surgery either with irradiated, IL-2 gene-modified MK16 tumour cells, or with recombinant IL-2.
141	14654953	Similarly, when the mice carrying TC-1 tumour residua after surgery were injected with recombinant GM-CSF, the recombinant GM-CSF inhibited growth of the tumour residua in the operated mice.
142	14654953	TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A and 8 days later, peritumourally, either with IL-2 gene-modified and IL-2-producing MK16 cells, or with recombinant IL-2.
143	14654953	TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A and then, peritumourally, either with irradiated, GM-CSF gene-modified and GM-CSF-producing MK16 cells, or with recombinant GM-CSF, it was found that both, the recombinant GM-CSF and GM-CSF gene therapy inhibited growth of tumour residua.
144	14654953	It has been found that both, recombinant IL-2 and GM-CSF, can inhibit growth of the tumour residua after surgery or chemotherapy.
145	14654953	The lung metastases in mice with surgical minimal residual tumour disease or in mice with tumour residua after chemotherapy were inhibited by IL-2 but not by GM-CSF.
146	14654953	In conclusion, the MHC class I+ and MHC class I-, HPV16-associated tumours were found to be sensitive to IL-2 and GM-CSF therapy after surgery or after cytoreductive chemotherapy.
147	14654953	Treatment of minimal residual disease after surgery or chemotherapy in mice carrying HPV16-associated tumours: Cytokine and gene therapy with IL-2 and GM-CSF.
148	14654953	Moderately immunogenic HPV16-associated tumours TC-1 (MHC class I+, HPV16 E6/E7+, G12V Ha-ras+) and MK16/1/IIIABC (MK16, MHC class I-, HPV16 E6/E7+, G12V Ha-ras+), both of the H-2b haplotype and transplanted in syngeneic mice, were used to examine the effects of local IL-2 and GM-CSF cytokine or gene therapy in the treatment of minimal residual tumour disease.
149	14654953	The mice carrying MHC class I+ TC-1 tumour residua after surgery were injected into the site of the surgery either with irradiated, IL-2 gene-modified MK16 tumour cells, or with recombinant IL-2.
150	14654953	Similarly, when the mice carrying TC-1 tumour residua after surgery were injected with recombinant GM-CSF, the recombinant GM-CSF inhibited growth of the tumour residua in the operated mice.
151	14654953	TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A and 8 days later, peritumourally, either with IL-2 gene-modified and IL-2-producing MK16 cells, or with recombinant IL-2.
152	14654953	TC-1 tumours were injected i.p. with ifosfamide derivative CBM-4A and then, peritumourally, either with irradiated, GM-CSF gene-modified and GM-CSF-producing MK16 cells, or with recombinant GM-CSF, it was found that both, the recombinant GM-CSF and GM-CSF gene therapy inhibited growth of tumour residua.
153	14654953	It has been found that both, recombinant IL-2 and GM-CSF, can inhibit growth of the tumour residua after surgery or chemotherapy.
154	14654953	The lung metastases in mice with surgical minimal residual tumour disease or in mice with tumour residua after chemotherapy were inhibited by IL-2 but not by GM-CSF.
155	14654953	In conclusion, the MHC class I+ and MHC class I-, HPV16-associated tumours were found to be sensitive to IL-2 and GM-CSF therapy after surgery or after cytoreductive chemotherapy.
156	14748438	For these purposes, we have used two oncogenic cell lines induced independently by co-transfection of murine H-2b cells with E61E7 HPV16 and activated Ha-ras oncogenes, the tumours TC-1 (MHC class I+, HPV16 E7+) and E7+).
157	14748438	Preimmunization with the MHC class I+ tumour did not protect against a subsequent challenge with the MHC class I- tumour and vice versa; however, immunization with the TC-1 tumour could protect syngeneic mice against the TC-1 tumour challenge and, similarly, immunization with the MK16/1/IIIABC tumour could protect mice against the MK16/1/IIIABC tumour challenge.
158	14748438	For these purposes, we have used two oncogenic cell lines induced independently by co-transfection of murine H-2b cells with E61E7 HPV16 and activated Ha-ras oncogenes, the tumours TC-1 (MHC class I+, HPV16 E7+) and E7+).
159	14748438	Preimmunization with the MHC class I+ tumour did not protect against a subsequent challenge with the MHC class I- tumour and vice versa; however, immunization with the TC-1 tumour could protect syngeneic mice against the TC-1 tumour challenge and, similarly, immunization with the MK16/1/IIIABC tumour could protect mice against the MK16/1/IIIABC tumour challenge.
160	14764678	DC release abundant MHC class I/peptide complexes transferred within exosomes to other naive DC for efficient CD8(+) T cell priming in vitro; 2). exosomes require nature's adjuvants (mature DC) to efficiently promote the differentiation of melanoma-specific effector T lymphocytes producing IFN-gamma (Tc1) effector lymphocytes in HLA-A2 transgenic mice (HHD2).
161	14971031	Dendritic cells generated in the presence of GM-CSF plus IL-15 prime potent CD8+ Tc1 responses in vivo.
162	14971031	DC progenitors can be stimulated to differentiate into immature DC by various growth factors, including GM-CSF and IL-4.
163	14971031	Here we show that IL-15, in combination with GM-CSF, is a growth factor for murine DC.
164	14971031	Murine bone marrow cells, depleted of T cells, B cells, I-A+ cells and Gr-1+ granulocytes, and cultured in the presence of GM-CSF plus IL-15 (IL-15 DC), yielded DC expressing high levels of CD11c and MHC class II molecules, as well as CD11b.
165	14971031	These cells expressed significant levels of CD40, CD80 and CD86, and could stimulate allogeneic CD4+ T cells efficiently.
166	14971031	Interestingly, IL-15 DC were far superior to DC generated with GM-CSF plus IL-4 in stimulating allogeneic CD8+ T cells in vitro.
167	14971031	Consistent with this, IL-15 DC induced much more potent antigen-specific CD8+ T cell responses with high levels of Th1 cytokines in vivo, compared to DC generated with GM-CSF plus IL-4, or with GM-CSF plus TGF-beta, or with GM-CSF alone.
168	14971031	Together, these data suggest that IL-15 promotes the development of DC, which induce potent Th1 and Tc1 responses in vivo.
169	14985791	These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat-shock protein 70 (HSP70), calreticulin (CRT) and the translocation domain (dII) of Pseudomonas aeruginosa exotoxin A (ETA).
170	14985791	Vaccination with DNA vaccines encoding E7 antigen linked to any of these molecules all led to a significant enhancement of E7-specific CD8(+) T-cell immune responses and strong antitumor effects against an E7-expressing tumor, TC-1.
171	15067049	A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells.
172	15067049	Thus, Escherichia coli LPS (TLR-4 stimulus), activates DCs to produce abundant IL-12(p70), but little IL-10, and stimulates Th1 and Tc1 responses.
173	15067049	In contrast, Pam-3-cys (TLR-2 stimulus) elicits less IL-12(p70), but abundant IL-10, and favors Th2 and T cytotoxic 2 (Tc2) responses.
174	15067049	Thus, Pam-3-cys induces enhanced extracellular signal-regulated kinase signaling, compared with LPS, resulting in suppressed IL-12(p70) and enhanced IL-10 production, as well as enhanced induction of the transcription factor, c-Fos.
175	15067049	Interestingly, DCs from c-fos(-/-) mice produce more IL-12(p70), but less IL-10, compared with control DCs.
176	15214037	A naked Sindbis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression.
177	15280455	We previously developed DNA vaccines encoding calreticulin (CRT) linked to HPV-16 E7 and generated potent E7-specific CD8(+) T-cell immune responses and antitumor effects against an E7-expressing tumor.
178	15280455	Our results indicated that the CRT/E6 DNA vaccine, but not a wild-type E6 DNA vaccine, generated significant E6-specific CD8(+) T-cell immune responses in vaccinated mice.
179	15280455	Vaccination with a CRT/E6 but not a CRT/mtE6 (lacking aa 50 to 57 of E6) DNA vaccine could protect vaccinated mice from challenge with E6-expressing TC-1 tumors.
180	15496603	FN had higher numbers and percentages of memory/effector (M/E) cytotoxic/suppressor (CD45R0(+)CD8(+), RMA) T, Fas(+) M/E (CD45R0(+)CD95(+)CD3(+), 6 mo) T, and CD56(+)CD16(-) NK cells (CD56(+)CD16(-)CD3(-)CD8(-), 12 mo), and higher percentages of M/E helper (CD45R0(+)CD4(+), RMA) T, Tc1 (IFN gamma(+)CD4(-)CD3(+), RMA), total interferon (IFN)gamma T (IFN gamma(+)CD4(+/-)CD3(+), RMA), Th2 (IL-4(+)CD4(+)CD3(+), 7 mo), and CD57(+) NK-T cells (CD57(+)CD56(-)CD3(+), 6 mo, 7 mo) compared with F.
181	15496603	Percentages of naive helper T (CD45RA(+)CD4(+), 12 mo) and numbers and percentages of CD56(+) NK-T cells (CD56(+)CD16(-)CD3(+)CD8(-), 2 mo, 6 mo) were lower in FN than F.
182	15496603	Percentages of M/E cytotoxic/suppressor, Th2, and CD56(+)CD16(-) NK cells in FN were significantly higher than F but were not different from HMF, whereas F was significantly lower than HMF.
183	15530672	Injection of a mixture of the synthetic HPV16-E7 protein and the synthetic adjuvant CpG in mice resulted in strong functional HPV16-specific cytotoxic T-lymphocyte responses as measured by CD8+ MHC class I-tetramer staining, the detection of antigen-specific intracellular IFNgamma production and the ability to protect mice against a challenge with HPV16-E7+ TC-1 tumour cells in both prophylactic and therapeutic vaccination regimens.
184	15542183	Cytotoxicity and interferon-gamma assays showed that spleenocytes from immunized animals were able to recognize and lyze E7 expressing tumor TC-1 cells.
185	15553669	Monocytes were separated from the peripheral blood collected by leukapheresis, and were cultured with GM-CSF and IL-4 for 6 days.
186	15553669	Then, TNF-alpha, IL-1beta, IL-6 and PGE2 were added for maturation of DC.
187	15553669	Th1/Th2 and Tc1/Tc2 balances improved in six of the nine patients after vaccination.
188	15553669	In this study, it was shown that immunosuppressive factors, such as IAP and TGF-beta, and Th1 balance are useful as markers of immunomonitoring for tumor-DC fusion vaccine in patients with advanced or recurrent gastrointestinal patients.
189	15926077	The Bordetella adenylate cyclase toxoid (CyaA) targets cells expressing the alphaMbeta2 integrin receptor CD11b/CD18 (CR3 or Mac-1) and can penetrate into cytosol of professional antigen-presenting cells, such as dendritic cells.
190	15926077	We show here that vaccination with a genetically detoxified CyaA336/E7 protein, carrying the full-length oncoprotein E7 of the human papilloma virus 16 inserted at position 336 of the cell-invasive AC domain of CyaA, induces an E7-specific CD8+ T-cell immune response and confers on mice protective, as well as therapeutic immunity against challenge with TC-1 tumor cells expressing the E7 oncoprotein.
191	15979942	An E7-expressing murine tumor model with a downregulated Fas expression--TC-1 P3(A15) tumors--was created.
192	15979942	A DNA vaccine encoding calreticulin linked to E7 (CRT/E7) was able to generate protective and therapeutic antitumor effects against TC-1 P3(A15) tumors.
193	15979942	In vitro Ab depletion and in vivo adoptive experiments showed that the antitumor effect of E7-specific CD8+ T lymphocytes against the TC-1 P3(A15) tumor cells was through the Fas-FasL-dependent CTL effector mechanism, and the TC-1 P3(A15) tumor cells needed higher numbers of antigen-specific CD8+ T lymphocytes for in vivo elimination.
194	15979942	Our results demonstrated that chimeric CRT/E7 DNA vaccine resulted in control of tumors with downregulated Fas expression, highlighting the importance of the Fas-FasL pathway in the potent antitumor effect of antigen-specific CD8+ cytotoxic T lymphocytes and the role of Fas as part of in vivo tumor evasion.
195	15979942	An E7-expressing murine tumor model with a downregulated Fas expression--TC-1 P3(A15) tumors--was created.
196	15979942	A DNA vaccine encoding calreticulin linked to E7 (CRT/E7) was able to generate protective and therapeutic antitumor effects against TC-1 P3(A15) tumors.
197	15979942	In vitro Ab depletion and in vivo adoptive experiments showed that the antitumor effect of E7-specific CD8+ T lymphocytes against the TC-1 P3(A15) tumor cells was through the Fas-FasL-dependent CTL effector mechanism, and the TC-1 P3(A15) tumor cells needed higher numbers of antigen-specific CD8+ T lymphocytes for in vivo elimination.
198	15979942	Our results demonstrated that chimeric CRT/E7 DNA vaccine resulted in control of tumors with downregulated Fas expression, highlighting the importance of the Fas-FasL pathway in the potent antitumor effect of antigen-specific CD8+ cytotoxic T lymphocytes and the role of Fas as part of in vivo tumor evasion.
199	15979942	An E7-expressing murine tumor model with a downregulated Fas expression--TC-1 P3(A15) tumors--was created.
200	15979942	A DNA vaccine encoding calreticulin linked to E7 (CRT/E7) was able to generate protective and therapeutic antitumor effects against TC-1 P3(A15) tumors.
201	15979942	In vitro Ab depletion and in vivo adoptive experiments showed that the antitumor effect of E7-specific CD8+ T lymphocytes against the TC-1 P3(A15) tumor cells was through the Fas-FasL-dependent CTL effector mechanism, and the TC-1 P3(A15) tumor cells needed higher numbers of antigen-specific CD8+ T lymphocytes for in vivo elimination.
202	15979942	Our results demonstrated that chimeric CRT/E7 DNA vaccine resulted in control of tumors with downregulated Fas expression, highlighting the importance of the Fas-FasL pathway in the potent antitumor effect of antigen-specific CD8+ cytotoxic T lymphocytes and the role of Fas as part of in vivo tumor evasion.
203	16107858	In this study, as a prelude to clinical translation, we characterized the ability of DNA-encoding calreticulin linked to DNA-encoding E7 antigen to generate HLA-A2-restricted E7-specific CD8(+) T-cell responses in HLA-A2 (AAD) transgenic mice, as well as antitumor effects against an E7(+) HLA-A2(+) tumor cell line, TC-1/A2.
204	16107858	Our results show that while vaccination with CRT/E7 DNA generates strong H-2D(b)-restricted E7 (amino acid (aa)49-57)-specific CD8(+) T-cell immune responses in both C57BL/6 and HLA-A2 (AAD) transgenic mice, no such responses were generated to HLA-A2-restricted epitopes in either type of mouse.
205	16107858	More importantly, vaccination with CRT/mtE7 (del aa49-57) DNA protects against a lethal challenge with TC-1/A2 tumor cells in HLA-A2 (AAD) transgenic mice.
206	16107858	Thus, the predominant E7 aa49-57-specific CD8+ T-cell immune response in HLA-A2 transgenic mice vaccinated with CRT/E7 is likely due to preferred expansion of E7 aa49-57-specific CD8(+) T cells in vaccinated mice.
207	16107858	In this study, as a prelude to clinical translation, we characterized the ability of DNA-encoding calreticulin linked to DNA-encoding E7 antigen to generate HLA-A2-restricted E7-specific CD8(+) T-cell responses in HLA-A2 (AAD) transgenic mice, as well as antitumor effects against an E7(+) HLA-A2(+) tumor cell line, TC-1/A2.
208	16107858	Our results show that while vaccination with CRT/E7 DNA generates strong H-2D(b)-restricted E7 (amino acid (aa)49-57)-specific CD8(+) T-cell immune responses in both C57BL/6 and HLA-A2 (AAD) transgenic mice, no such responses were generated to HLA-A2-restricted epitopes in either type of mouse.
209	16107858	More importantly, vaccination with CRT/mtE7 (del aa49-57) DNA protects against a lethal challenge with TC-1/A2 tumor cells in HLA-A2 (AAD) transgenic mice.
210	16107858	Thus, the predominant E7 aa49-57-specific CD8+ T-cell immune response in HLA-A2 transgenic mice vaccinated with CRT/E7 is likely due to preferred expansion of E7 aa49-57-specific CD8(+) T cells in vaccinated mice.
211	16138121	We tested the role of replication-incompetent recombinant herpes simplex virus (HSV) d106 lacking all immediate early genes except ICP0 in the generation of apoptotic cells for tumor vaccination, using ID8-VEGF, a syngeneic mouse model of ovarian carcinoma expressing high levels of VEGF, and TC-1, a human papillomavirus (HPV) 16 E6- and E7-transformed adenocarcinoma.
212	16200349	These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat shock protein 70 (HSP70), calreticulin (CRT) and herpes simplex virus type 1 (HSV-1) VP22 proteins.
213	16200349	In the current study, we have characterized DNA vaccines employing these intracellular targeting or intercellular spreading strategies targeting HPV-16 E6 for their ability to generate E6-specific CD8+ T cell immune responses and antitumor effects against an E6-expressing tumor cell line, TC-1, in C57BL/6 mice.
214	16200349	We found that all the intracellular targeting strategies (CRT, LAMP-1, HSP70) as well as the intercellular spreading strategy (VP22) were able to enhance E6 DNA vaccine potency, although the orientation of HSP70 linked to E6 antigen in the E6 DNA vaccine appears to be important for the HSP70 strategy to work.
215	16200349	The enhanced E6-specific CD8+ T cell immune response in vaccinated mice also translated into potent antitumor effects against TC-1 tumor cells.
216	16200349	These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat shock protein 70 (HSP70), calreticulin (CRT) and herpes simplex virus type 1 (HSV-1) VP22 proteins.
217	16200349	In the current study, we have characterized DNA vaccines employing these intracellular targeting or intercellular spreading strategies targeting HPV-16 E6 for their ability to generate E6-specific CD8+ T cell immune responses and antitumor effects against an E6-expressing tumor cell line, TC-1, in C57BL/6 mice.
218	16200349	We found that all the intracellular targeting strategies (CRT, LAMP-1, HSP70) as well as the intercellular spreading strategy (VP22) were able to enhance E6 DNA vaccine potency, although the orientation of HSP70 linked to E6 antigen in the E6 DNA vaccine appears to be important for the HSP70 strategy to work.
219	16200349	The enhanced E6-specific CD8+ T cell immune response in vaccinated mice also translated into potent antitumor effects against TC-1 tumor cells.
220	16207532	Experimental approaches to mediate GVT effects while limiting GVHD include: (1) allograft T cell depletion followed by immune enhancement; (2) modulation of T cell dose or T cell subset composition; (3) donor lymphocyte infusion; (4) reduced-intensity host preparation; (5) modulation of Th1/Th2 and Tc1/Tc2 cell balance; (6) cytokine therapy or neutralization; (7) T regulatory cell therapy; (8) co-stimulatory pathway modulation; (9) chemokine pathway modulation; (10) induction of antigen-specific T cells; (11) alloreactive NK cell therapy; and (12) targeted pharmaceutical inhibition of proteosome, mammalian target of rapamycin, and histone deacetylase pathways.
221	16306600	Th-cytotoxic T-lymphocyte chimeric epitopes extended by Nepsilon-palmitoyl lysines induce herpes simplex virus type 1-specific effector CD8+ Tc1 responses and protect against ocular infection.
222	16306600	As a model antigen, the HSV-1 glycoprotein B498-505 (gB498-505) CD8+ CTL epitope was synthesized in line with the Pan DR peptide (PADRE), a universal CD4+ Th epitope.
223	16306600	The palmitoyl-tailed Th-CTL chimeric epitopes provoked cell surface expression of major histocompatibility complex and costimulatory molecules and production of interleukin-12 and tumor necrosis factor alpha proinflammatory cytokines by immature dendritic cells.
224	16308571	Here, we show that plasmid DNA vaccination with a cassette encoding antigen (OVA) and a second cassette encoding full-length CD40 ligand (CD40L), a molecule expressed on activated CD4+ T lymphocytes and critical for T cell helper function, can elicit significant titers of antigen-specific immunoglobulins in serum and Tc1 CD8+ T cell responses in CD4-deficient mice.
225	16308571	To investigate whether this approach leads to CD4+ T cell-independent vaccine protection against a prototypic AIDS-defining infection, Pneumocystis (PC) pneumonia, we used serum from mice vaccinated with PC-pulsed, CD40L-modified DCs to immunoprecipitate PC antigens.
226	16308571	CD4-deficient mice receiving DNA vaccines encoding Kexin and CD40L showed significantly higher anti-PC IgG titers as well as opsonic killing of PC compared with those vaccinated with Kexin alone.
227	16328003	Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD).
228	16328003	It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants.
229	16328003	This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy.
230	16328003	This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours.
231	16328003	When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted.
232	16328003	Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD).
233	16328003	It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants.
234	16328003	This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy.
235	16328003	This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours.
236	16328003	When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted.
237	16328003	Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD).
238	16328003	It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants.
239	16328003	This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy.
240	16328003	This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours.
241	16328003	When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted.
242	16328003	Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD).
243	16328003	It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants.
244	16328003	This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy.
245	16328003	This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours.
246	16328003	When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted.
247	16328003	Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD).
248	16328003	It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants.
249	16328003	This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy.
250	16328003	This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours.
251	16328003	When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted.
252	16461338	Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-alpha.
253	16461338	Furthermore, distinct TLRs appear to differentially control the Th1/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D.
254	16844231	It does so by linking E7 with the sorting signal of lysosome-associated membrane protein 1 (Sig/LAMP-1) to enhance the presentation of E7 antigen to MHC class I-restricted CD8(+) T cells, as well as to MHC class II-restricted CD4(+) T cells.
255	16844231	In immunological studies, DC-Sig/E7/LAMP-1 dramatically increased in vitro activation and in vivo expansion of E7-specific CD4(+) and CD8(+) T cells, compared with DC-E7 and DC-No insert.
256	16844231	More importantly, in both tumor prevention and tumor treatment assays, DC-Sig/E7/LAMP-1 generated greater anti-tumor immunity against TC-1 than DC-E7.
257	16861891	Vaccine efficacy was tested in TC-1, a murine adenocarcinoma transformed with HPV16 E6 and E7, and ID8-Vegf, a murine epithelial ovarian cancer model.
258	17291642	Significant levels of IFN-gamma production by both CD4 and CD8 cells were observed along with CTL responses that were effective against both peptide-pulsed targets as well as syngeneic tumor cells (TC-1) expressing the cognate E6 and E7 proteins.
259	17291642	Furthermore, mice immunized with the peptide mixture and CT-2* effectively resisted TC-1 tumor challenge.
260	17291642	Significant levels of IFN-gamma production by both CD4 and CD8 cells were observed along with CTL responses that were effective against both peptide-pulsed targets as well as syngeneic tumor cells (TC-1) expressing the cognate E6 and E7 proteins.
261	17291642	Furthermore, mice immunized with the peptide mixture and CT-2* effectively resisted TC-1 tumor challenge.
262	17631051	Toward the development of multi-epitope p53 cancer vaccines: an in vitro assessment of CD8(+) T cell responses to HLA class I-restricted wild-type sequence p53 peptides.
263	17631051	Peripheral blood mononuclear cells (PBMC) obtained from HLA-A0201(+) and/or HLA-A2402(+) normal donors and subjects with squamous cell carcinoma of the head and neck (SCCHN) were analyzed for p53 peptide-specific reactivity in ELISPOT IFN-gamma assays.
264	17631051	CD8(+) T cells in 7/10 normal donors (HD) and 11/23 subjects with SCCHN responded to at least one of the wt p53 peptides.
265	17631051	CD8(+) T cell precursors responsive to wt p53 epitopes were detected in the circulation of most subjects with early disease, and an elevated blood Tc(1)/Tc(2) ratio distinguished wt p53 peptide responders from non-responders.
266	17785832	CD8+ T cell protective immunity against Chlamydia pneumoniae includes an H2-M3-restricted response that is largely CD4+ T cell-independent.
267	17785832	Recently, we reported that type 1 CD8+ (Tc1) from Cpn-infected B6 mice recognize peptides from multiple Cpn Ags in a classical MHC class Ia-restricted fashion.
268	17785832	H2-M3-binding peptides representing the N-terminal formylated sequences from five Cpn Ags sensitized target cells for lysis by cytolytic effectors from the spleens of infected B6 mice.
269	17785832	Of these, only peptides fMFFAPL (P1) and fMLYWFL (P4) stimulated IFN-gamma production by infection-primed splenic and pulmonary CD8+ T cells.
270	17785832	Finally, we show that in the absence of MHC class Ia-restricted CD8+ T cell responses, CD4+ T cells are largely expendable for the control of Cpn growth, and for the generation, memory maintenance, and secondary expansion of P1- and P4-specific CD8+ T cells.
271	17875726	Targeting the human papillomavirus (HPV) E7 antigen to dendritic cells with the adenylate cyclase (CyaA) of Bordetella pertussis as a vaccine vector led to potent therapeutic immune responses against TC-1 tumors in a murine model of cervical carcinoma induced by HPV.
272	17931752	Here, we show that C57BL/6 mice vaccinated with SCT-E6 DNA combined with antiapoptotic protein Bcl-xL DNA generated enhanced E6-specific CD8(+) T cell immune responses compared to mice vaccinated with SCT-E6 DNA and a non-functional mutant Bcl-xL (mtBcl-xL) DNA.
273	17931752	Furthermore, we show that mice treated with SCT-E6 and Bcl-xL DNA generated enhanced anti-tumor effects against E6-expressing tumor cells (TC-1/Luciferase) compared to mice treated with SCT-E6 and mtBcl-xL DNA.
274	18202774	In the spleens of TC-1 (MHC class I+) but not of TC-1/A9 (MHC class I-) treated tumour-bearing animals, the cytotoxic CD8+ cells detectable in 51Cr microcytotoxicity assay, were found.
275	18202774	Down-regulation of the CD4+ and CD8+ subpopulations in spleens of tumour-bearing animals were not restored after therapy.
276	18202774	The percentage of CD25+/CD4+ T regulatory (Treg) cells in lymph nodes remained unchanged.
277	18317362	Given the perceived need to augment antitumor type-1 immunity (TC1 and Th1) as a therapeutic end point, and the known functional plasticity of DC populations that may display heterogeneous capacity to promote T-cell responses, we sought to identify a preferred DC preparation with this capacity.
278	18317362	We compared 2 different preparations of monocyte-derived DC using interferon-alpha (IFN-alpha) (IFN-DC and alphaDC1) with classic DCs "matured" (mDCs) using interleukin-1beta/interleukin-6/tumor necrosis factor-alpha/prostaglandin E2, for their ability to promote autologous TC1 antitumor responses from RCC patients in vitro.
279	18317362	IFN-alpha-conditioned DC promoted significantly higher numbers of RCC-specific CD8+ T cells exhibiting a cytotoxic phenotype after in vitro stimulation (IVS) than cytokine cocktail-mDCs.
280	18453624	The MHC CIITA is a master regulator of MHC class II expression and also induces expression of class I molecules.
281	18453624	Furthermore, our data suggested that coadministration of DNA-encoding calreticulin (CRT) linked to human papillomavirus (HPV) 16 E6 Ag (CRT/E6) with CIITA DNA leads to enhanced E6-specific CD8(+) T cell immune responses in vaccinated mice.
282	18453624	In addition, coadministration of the combination of CRT/E6 DNA with CIITA DNA and DNA encoding the invariant chain (Ii) linked to the pan HLA-DR-reactive epitope (Ii-PADRE) further enhanced E6-specific CD8(+) T cell immune responses in vaccinated mice.
283	18453624	Vaccination with the combination vaccine also led to enhanced E6-specific CD8(+) memory T cells and to long-term protection against TC-1 tumors and prolonged survival in vaccinated mice.
284	18453624	Thus, our findings suggest that the combination of CIITA DNA with CRT/E6 and Ii-PADRE DNA vaccines represents a potentially effective means to combat tumors in the clinical setting.
285	18463686	We observed that pretreatment with doxorubicin suppressed the E6-specific CD8+ T-cell immune responses generated by CRT/E6 DNA vaccination in vaccinated mice.
286	18463686	Furthermore, coadministration of Ii-PADRE DNA could not only reverse the suppression, but also enhanced the E6-specific CD8+ T-cell responses in CRT/E6-vaccinated mice pretreated with doxorubicin.
287	18463686	Finally, treatment with doxorubicin followed by CRT/E6 combined with Ii-PADRE DNA vaccination led to enhanced antitumor effects and prolonged survival in TC-1 tumor-bearing mice.
288	18542898	We found that the combination of treatment with bortezomib and CRT/E7(detox) DNA generated more potent E7-specific CD8+ T cell immune responses and better therapeutic effects against TC-1 tumors in tumor-bearing mice compared to monotherapy.
289	18542898	Furthermore, we found that treatment with bortezomib led to increased apoptosis of TC-1 tumor cells and could render the TC-1 tumor cells more susceptible to lysis by E7-specific CD8+ T cells.
290	18542898	We found that the combination of treatment with bortezomib and CRT/E7(detox) DNA generated more potent E7-specific CD8+ T cell immune responses and better therapeutic effects against TC-1 tumors in tumor-bearing mice compared to monotherapy.
291	18542898	Furthermore, we found that treatment with bortezomib led to increased apoptosis of TC-1 tumor cells and could render the TC-1 tumor cells more susceptible to lysis by E7-specific CD8+ T cells.
292	18598733	Our results indicated that mice bearing the E7-expressing tumor, TC-1 treated with MD5-1 monoclonal antibody followed by CRT/E7(detox) DNA vaccination generated the most potent therapeutic anti-tumor effects as well as highest levels of E7-specific CD8+ T cells among all the groups tested.
293	18636165	The effect of the treatment was not enhanced by the simultaneous administration of non-oncogenic, genetically modified TC-1 cells expressing either IL-2, IL-12 or GM-CSF, and, in fact, the oncolytic effect of the virus was even less expressed in some instances.
294	18940198	While it is well established that CD4(+) T lymphocytes play a crucial role in the initiation, progression and persistence of asthma, the role of CD8(+) T cells is less understood.
295	18940198	CD8(+) T cells form functionally similar subsets which exhibit similar cytokine profiles as Th1 and Th2 cells, known as Tc1 and Tc2.
296	18940198	Evidence from animal studies suggest that CD8(+) T cells are capable of regulating IgE production through the induction of IL-12 and IL-18 production in dendritic cells, and that CD8(+) T cells may act to moderate Th2 polarisation within the localised lymph nodes during allergic sensitisation.
297	19056449	Enhancing therapeutic HPV DNA vaccine potency through depletion of CD4+CD25+ T regulatory cells.
298	19056449	We found that administration of PC61 prior to vaccination with E7/Hsp70 DNA was capable of generating higher levels of E7-specific CD8(+) T cells compared to the control antibody, leading to significantly improved therapeutic and long-term protective antitumor effects against an E7-expressing tumor, TC-1.
299	19056449	Thus, a strategy to deplete CD4(+)CD25(+) Tregs in conjunction with therapeutic tumor antigen-specific DNA vaccine may represent a potentially promising approach to control tumor.
300	19082488	The chemotherapy resulted in the decrease of the CD4+ and CD8+ TIL, increase of the Gr-1+/CD11b+ TIL, no changes in the infiltration with CD4+/CD25+ Treg TIL, and decrease of the cytolytic and proliferative potential of the CD45+ TIL.
301	19082488	Subsequent immunotherapy with the IL-12-producing, genetically modified TC-1 (TC-1-IL-12) cells increased tumour infiltration with CD8+ and CD4+ cells, decreased the Gr-1+/CD11b+ cells, and increased the cytolytic and proliferative potential of the CD45+ TIL.
302	19739073	Treatment of tumor-bearing mice with beta-GalCer(C12) 3-14 days after tumor cell transplantation significantly inhibited the growth of the major histocompatibility complex (MHC) Class I-positive (TC-1), as well as MHC Class I-deficient (TC-1/A9) HPV16-associated tumors.
303	19816937	TC-1 tumors and that tumor regression was mainly provided by CD8 T cells.
304	19863514	Intradermal injections of polyarginine-containing immunogenic antigens preferentially elicit Tc1 and Th1 activation and antitumour immunity.
305	19863514	Background We previously have shown that nona-arginine protein transduction domain (R9-PTD) induced efficient protein-antigen (Ag) transduction of dendritic cells (DCs) in vitro, resulting in the efficient induction of strong Ag-specific immune responses mediated by CD8+ and CD4+ T cells and in superior antitumour effects in vivo in cancer-bearing mice.
306	19863514	The i.d. injections of rR9-OVA also induced inflammatory cell infiltrates containing neutrophils, monocytes and lymphocytes, as well as production of inflammatory cytokines such as interferon (IFN)-gamma, interleukin-2 and IFN-inducible protein 10, with presenting SIINFEKL epitopes on major histocompatibility complex (MHC) class I molecules at the injection area. i.t. injections of rR9-OVA into EG.7 tumour mass significantly suppressed tumour growth, and these effects were completely abrogated by the depletion of CD8+ T cells.
307	19923459	Soluble B and T lymphocyte attenuator possesses antitumor effects and facilitates heat shock protein 70 vaccine-triggered antitumor immunity against a murine TC-1 cervical cancer model in vivo.
308	19923459	B and T lymphocyte attenuator (BTLA)-herpesvirus entry mediator (HVEM) signaling coinhibitory pathway is believed to impair antitumor immune competences.
309	19923459	To address this issue, we constructed a eukaryotic expression plasmid (psBTLA) that expressed the extracellular domain of murine BTLA (soluble form of BTLA), which could bind HVEM, the ligand of BTLA, and block BTLA-HVEM interactions.
310	19923459	The data in this study showed that treatment by injection of psBTLA resulted in down-regulation of IL-10 and TGF-beta and promotion of dendritic cell function by increasing the expression of B7-1 and IL-12, but the adaptive antitumor immune responses achieved by psBTLA administration alone were limited and could not eradicate the tumor effectively.
311	19923459	Next, we evaluated the immunotherapeutic efficacy and mechanism of combination therapy of heat shock protein 70 (HSP70) vaccine/psBTLA by using murine TC-1 cervical cancer mice as an ectopic tumor model.
312	19923459	Our in vivo studies revealed that treatment with HSP70 vaccine alone did not lead to satisfactory tumor growth inhibition, whereas cotreatment with psBTLA significantly improved antitumor immunity and compensated the deficiency of HSP70 vaccine by increasing the expression of Th1 cytokines, IL-2, and IFN-gamma and decreasing transcription levels of IL-10, TGF-beta, and Foxp3 in the tumor microenvironment.
313	19923459	Soluble B and T lymphocyte attenuator possesses antitumor effects and facilitates heat shock protein 70 vaccine-triggered antitumor immunity against a murine TC-1 cervical cancer model in vivo.
314	19923459	B and T lymphocyte attenuator (BTLA)-herpesvirus entry mediator (HVEM) signaling coinhibitory pathway is believed to impair antitumor immune competences.
315	19923459	To address this issue, we constructed a eukaryotic expression plasmid (psBTLA) that expressed the extracellular domain of murine BTLA (soluble form of BTLA), which could bind HVEM, the ligand of BTLA, and block BTLA-HVEM interactions.
316	19923459	The data in this study showed that treatment by injection of psBTLA resulted in down-regulation of IL-10 and TGF-beta and promotion of dendritic cell function by increasing the expression of B7-1 and IL-12, but the adaptive antitumor immune responses achieved by psBTLA administration alone were limited and could not eradicate the tumor effectively.
317	19923459	Next, we evaluated the immunotherapeutic efficacy and mechanism of combination therapy of heat shock protein 70 (HSP70) vaccine/psBTLA by using murine TC-1 cervical cancer mice as an ectopic tumor model.
318	19923459	Our in vivo studies revealed that treatment with HSP70 vaccine alone did not lead to satisfactory tumor growth inhibition, whereas cotreatment with psBTLA significantly improved antitumor immunity and compensated the deficiency of HSP70 vaccine by increasing the expression of Th1 cytokines, IL-2, and IFN-gamma and decreasing transcription levels of IL-10, TGF-beta, and Foxp3 in the tumor microenvironment.
319	19940864	We found that the co-administration of a DNA vaccine in conjunction with a DNA encoding a xenogenic major histocompatibility complex (MHC) molecule could significantly enhance the E7-specific CD8+ T-cell immune responses and antitumor effects against an E7-expressing tumor, TC-1, in C57BL/6 tumor-bearing mice.
320	19950168	Here, we demonstrated that utilizing nonlytic Fc-fused IL-7 (IL-7-Fc(m)) as a genetic adjuvant significantly enhanced not only CD4(+) but also CD8(+) T-cell responses by E7 DNA immunization, in addition to improving protection against TC-1-induced tumors in comparison to IL-7 alone.
321	19950168	Thus, our findings suggest that nonlytic Fc, in contrast to lytic Fc, fusion to cytokines may provide an insight in designing a potent genetic adjuvant for inducing CD4(+) and CD8(+) T-cell responses.
322	20406989	Conjugate vaccines containing human papillomavirus 16 E7 oncoprotein or survivin as a self-TAA had potent therapeutic efficacy against TC-1 cervical and 3LL lung carcinoma tumors, respectively.
323	20406989	Therapeutic efficacy of the vaccines was associated with increased CD4(+) T and CD8(+) T-cell effector and memory responses and higher intratumoral CD8(+) T effector/CD4(+)CD25(+)Foxp3(+) T regulatory cell ratio.
324	20473939	Besides, a favorable host environment was created by the reduced secretion of interleukin-10 and 6 and vascular endothelial growth factor (VEGF) in the tumor niche and decreased the expression of phosphorylation-signal transducer and activator of transcription 3 of TC-1 tumors.
325	20549206	Poly-ICLC promotes the infiltration of effector T cells into intracranial gliomas via induction of CXCL10 in IFN-alpha and IFN-gamma dependent manners.
326	20549206	In this study, we sought to determine critical roles of host IFN-alpha and IFN-gamma pathways in the enhanced therapeutic efficacy mediated by peptide vaccines and polyinosinic-polycytidylic acid [poly(I:C)] stabilized by lysine and carboxymethylcellulose (poly-ICLC) in the murine central nervous system (CNS) GL261 glioma.
327	20549206	C57BL/6-background wild type (WT), IFN-alpha receptor-1 (IFN-alphaR1)(-/-) or IFN-gamma(-/-) mice bearing syngeneic CNS GL261 glioma received subcutaneous (s.c.) vaccinations with synthetic peptides encoding CTL epitopes with or without intramuscular (i.m.) injections of poly-ICLC.
328	20549206	Both IFN-alphaR(-/-) and IFN-gamma(-/-) hosts failed to up-regulate the CXCL10 mRNA and recruit Tc1 cells to the tumor site, indicating non-redundant roles of type-1 and type-2 IFNs in the effects of poly-ICLC-assisted vaccines.
329	20549206	The efficient trafficking of Tc1 also required Tc1-derived IFN-gamma.
330	20549206	Our data point to critical roles of the host-IFN-alpha and IFN-gamma pathways in the modulation of CNS glioma microenvironment, and the therapeutic effectiveness of poly-ICLC-assisted glioma vaccines.
331	20713880	T-bet and Eomesodermin (Eomes) have been suggested to be master regulators of Th1 cells and CD8(+) T cells.
332	20713880	T-bet and Eomes drive Tc1 differentiation by preventing alternative CD8(+) T cell differentiation to Tc17 or Tc2 cells.
333	20713880	Surprisingly, T-bet and Eomes are not critical for the generation of systemic CTL activities against cancer cells.
334	20713880	Instead, T-bet and Eomes are crucial for tumor infiltration by CD8(+) T cells.
335	20713880	This study defines T-bet and Eomes as critical regulators of T cell-mediated immune responses against tumor.
336	20739505	Recombinant adenovirus or DNA vaccines encoding herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) genetically fused to human papillomavirus type 16 (HPV-16) oncoproteins (E5, E6, and E7) induce antigen-specific CD8(+) T-cell responses and confer preventive resistance to transplantable murine tumor cells (TC-1 cells).
337	20739505	In the present report, we characterized some previously uncovered aspects concerning the induction of CD8(+) T-cell responses and the therapeutic anticancer effects achieved in C57BL/6 mice immunized with pgD-E7E6E5 previously challenged with TC-1 cells.
338	20739505	Concerning the characterization of the immune responses elicited in mice vaccinated with pgD-E7E6E5, we determined the effect of the CD4(+) T-cell requirement, longevity, and dose-dependent activation on the E7-specific CD8(+) T-cell responses.
339	20739505	Mice challenged with TC-1 cells and then immunized with three doses of pgD-E7E6E5 elicited CD8(+) T-cell responses, measured by intracellular gamma interferon (IFN-γ) and CD107a accumulation, to the three HPV-16 oncoproteins and displayed in vivo antigen-specific cytolytic activity, as demonstrated with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled target cells pulsed with oligopeptides corresponding to the H-2D(b)-restricted immunodominant epitopes of the E7, E6, or E5 oncoprotein.
340	20739505	In addition, coadministration of pgD-E7E6E5 with DNA vectors encoding pGM-CSF or interleukin-12 (IL-12) enhanced the therapeutic antitumor effects for all mice challenged with TC-1 cells.
341	20739505	Recombinant adenovirus or DNA vaccines encoding herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) genetically fused to human papillomavirus type 16 (HPV-16) oncoproteins (E5, E6, and E7) induce antigen-specific CD8(+) T-cell responses and confer preventive resistance to transplantable murine tumor cells (TC-1 cells).
342	20739505	In the present report, we characterized some previously uncovered aspects concerning the induction of CD8(+) T-cell responses and the therapeutic anticancer effects achieved in C57BL/6 mice immunized with pgD-E7E6E5 previously challenged with TC-1 cells.
343	20739505	Concerning the characterization of the immune responses elicited in mice vaccinated with pgD-E7E6E5, we determined the effect of the CD4(+) T-cell requirement, longevity, and dose-dependent activation on the E7-specific CD8(+) T-cell responses.
344	20739505	Mice challenged with TC-1 cells and then immunized with three doses of pgD-E7E6E5 elicited CD8(+) T-cell responses, measured by intracellular gamma interferon (IFN-γ) and CD107a accumulation, to the three HPV-16 oncoproteins and displayed in vivo antigen-specific cytolytic activity, as demonstrated with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled target cells pulsed with oligopeptides corresponding to the H-2D(b)-restricted immunodominant epitopes of the E7, E6, or E5 oncoprotein.
345	20739505	In addition, coadministration of pgD-E7E6E5 with DNA vectors encoding pGM-CSF or interleukin-12 (IL-12) enhanced the therapeutic antitumor effects for all mice challenged with TC-1 cells.
346	20739505	Recombinant adenovirus or DNA vaccines encoding herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) genetically fused to human papillomavirus type 16 (HPV-16) oncoproteins (E5, E6, and E7) induce antigen-specific CD8(+) T-cell responses and confer preventive resistance to transplantable murine tumor cells (TC-1 cells).
347	20739505	In the present report, we characterized some previously uncovered aspects concerning the induction of CD8(+) T-cell responses and the therapeutic anticancer effects achieved in C57BL/6 mice immunized with pgD-E7E6E5 previously challenged with TC-1 cells.
348	20739505	Concerning the characterization of the immune responses elicited in mice vaccinated with pgD-E7E6E5, we determined the effect of the CD4(+) T-cell requirement, longevity, and dose-dependent activation on the E7-specific CD8(+) T-cell responses.
349	20739505	Mice challenged with TC-1 cells and then immunized with three doses of pgD-E7E6E5 elicited CD8(+) T-cell responses, measured by intracellular gamma interferon (IFN-γ) and CD107a accumulation, to the three HPV-16 oncoproteins and displayed in vivo antigen-specific cytolytic activity, as demonstrated with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled target cells pulsed with oligopeptides corresponding to the H-2D(b)-restricted immunodominant epitopes of the E7, E6, or E5 oncoprotein.
350	20739505	In addition, coadministration of pgD-E7E6E5 with DNA vectors encoding pGM-CSF or interleukin-12 (IL-12) enhanced the therapeutic antitumor effects for all mice challenged with TC-1 cells.
351	20739505	Recombinant adenovirus or DNA vaccines encoding herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) genetically fused to human papillomavirus type 16 (HPV-16) oncoproteins (E5, E6, and E7) induce antigen-specific CD8(+) T-cell responses and confer preventive resistance to transplantable murine tumor cells (TC-1 cells).
352	20739505	In the present report, we characterized some previously uncovered aspects concerning the induction of CD8(+) T-cell responses and the therapeutic anticancer effects achieved in C57BL/6 mice immunized with pgD-E7E6E5 previously challenged with TC-1 cells.
353	20739505	Concerning the characterization of the immune responses elicited in mice vaccinated with pgD-E7E6E5, we determined the effect of the CD4(+) T-cell requirement, longevity, and dose-dependent activation on the E7-specific CD8(+) T-cell responses.
354	20739505	Mice challenged with TC-1 cells and then immunized with three doses of pgD-E7E6E5 elicited CD8(+) T-cell responses, measured by intracellular gamma interferon (IFN-γ) and CD107a accumulation, to the three HPV-16 oncoproteins and displayed in vivo antigen-specific cytolytic activity, as demonstrated with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled target cells pulsed with oligopeptides corresponding to the H-2D(b)-restricted immunodominant epitopes of the E7, E6, or E5 oncoprotein.
355	20739505	In addition, coadministration of pgD-E7E6E5 with DNA vectors encoding pGM-CSF or interleukin-12 (IL-12) enhanced the therapeutic antitumor effects for all mice challenged with TC-1 cells.
356	20817010	Therefore, priming with a DNA vaccine in the presence of α-GalCer and boosting with E7-pulsed DC-1 led to a significant enhancement of E7-specific CD8(+) effector and memory T-cells as well as significantly improved therapeutic and preventive effects against an E7-expressing tumor model (TC-1) in vaccinated mice.
357	21109988	In vivo depletion of CD8+ cells, but not of CD4+ or NK1.1+ cells in the immunization period resulted in complete elimination of the protective effects of immunization with irradiated TC-1 cells (MHC class I-positive cell line) against the TC-1 tumour challenge.
358	21109988	After immunization with irradiated TC-1/A9 or with MK16 tumour cells (MHC class I-deficient sublines) a remarkable dependence on the presence of NK1.1+ cells was observed, while the tumour growth inhibition after CD4+ or CD8+ depletion was not efficient.
359	21109988	Cytotoxic activity induced by TC-1 cell immunization was significantly abrogated in the CD8+ and CD4+ but not NK1.1+ cell-depleted mice, as compared to the immunized only controls.
360	21109988	After MK16 or TC-1/A9 cell immunization, NK1.1+ but not CD8+ and CD4+ cell-depleted mice displayed significant reduction of specific cytotoxicity.
361	21109988	Mice immunized with TC-1 cells showed similar percentage of IFNγ producing cells in CD8+, CD4+ and NK1.1+ cell populations.
362	21109988	In vivo depletion of CD8+ cells, but not of CD4+ or NK1.1+ cells in the immunization period resulted in complete elimination of the protective effects of immunization with irradiated TC-1 cells (MHC class I-positive cell line) against the TC-1 tumour challenge.
363	21109988	After immunization with irradiated TC-1/A9 or with MK16 tumour cells (MHC class I-deficient sublines) a remarkable dependence on the presence of NK1.1+ cells was observed, while the tumour growth inhibition after CD4+ or CD8+ depletion was not efficient.
364	21109988	Cytotoxic activity induced by TC-1 cell immunization was significantly abrogated in the CD8+ and CD4+ but not NK1.1+ cell-depleted mice, as compared to the immunized only controls.
365	21109988	After MK16 or TC-1/A9 cell immunization, NK1.1+ but not CD8+ and CD4+ cell-depleted mice displayed significant reduction of specific cytotoxicity.
366	21109988	Mice immunized with TC-1 cells showed similar percentage of IFNγ producing cells in CD8+, CD4+ and NK1.1+ cell populations.
367	21109988	In vivo depletion of CD8+ cells, but not of CD4+ or NK1.1+ cells in the immunization period resulted in complete elimination of the protective effects of immunization with irradiated TC-1 cells (MHC class I-positive cell line) against the TC-1 tumour challenge.
368	21109988	After immunization with irradiated TC-1/A9 or with MK16 tumour cells (MHC class I-deficient sublines) a remarkable dependence on the presence of NK1.1+ cells was observed, while the tumour growth inhibition after CD4+ or CD8+ depletion was not efficient.
369	21109988	Cytotoxic activity induced by TC-1 cell immunization was significantly abrogated in the CD8+ and CD4+ but not NK1.1+ cell-depleted mice, as compared to the immunized only controls.
370	21109988	After MK16 or TC-1/A9 cell immunization, NK1.1+ but not CD8+ and CD4+ cell-depleted mice displayed significant reduction of specific cytotoxicity.
371	21109988	Mice immunized with TC-1 cells showed similar percentage of IFNγ producing cells in CD8+, CD4+ and NK1.1+ cell populations.
372	21109988	In vivo depletion of CD8+ cells, but not of CD4+ or NK1.1+ cells in the immunization period resulted in complete elimination of the protective effects of immunization with irradiated TC-1 cells (MHC class I-positive cell line) against the TC-1 tumour challenge.
373	21109988	After immunization with irradiated TC-1/A9 or with MK16 tumour cells (MHC class I-deficient sublines) a remarkable dependence on the presence of NK1.1+ cells was observed, while the tumour growth inhibition after CD4+ or CD8+ depletion was not efficient.
374	21109988	Cytotoxic activity induced by TC-1 cell immunization was significantly abrogated in the CD8+ and CD4+ but not NK1.1+ cell-depleted mice, as compared to the immunized only controls.
375	21109988	After MK16 or TC-1/A9 cell immunization, NK1.1+ but not CD8+ and CD4+ cell-depleted mice displayed significant reduction of specific cytotoxicity.
376	21109988	Mice immunized with TC-1 cells showed similar percentage of IFNγ producing cells in CD8+, CD4+ and NK1.1+ cell populations.
377	21109988	In vivo depletion of CD8+ cells, but not of CD4+ or NK1.1+ cells in the immunization period resulted in complete elimination of the protective effects of immunization with irradiated TC-1 cells (MHC class I-positive cell line) against the TC-1 tumour challenge.
378	21109988	After immunization with irradiated TC-1/A9 or with MK16 tumour cells (MHC class I-deficient sublines) a remarkable dependence on the presence of NK1.1+ cells was observed, while the tumour growth inhibition after CD4+ or CD8+ depletion was not efficient.
379	21109988	Cytotoxic activity induced by TC-1 cell immunization was significantly abrogated in the CD8+ and CD4+ but not NK1.1+ cell-depleted mice, as compared to the immunized only controls.
380	21109988	After MK16 or TC-1/A9 cell immunization, NK1.1+ but not CD8+ and CD4+ cell-depleted mice displayed significant reduction of specific cytotoxicity.
381	21109988	Mice immunized with TC-1 cells showed similar percentage of IFNγ producing cells in CD8+, CD4+ and NK1.1+ cell populations.
382	21228885	In this study, we demonstrated that intratumoral (i.t.) injection of MSCs expressing modified interleukin-12 (MSCs/IL-12M) exhibited stronger tumor-specific T-cell responses and antitumor effects as well as more sustained expressions of IL-12 and interferon (IFN)-γ in both sera and tumor sites than did IL-12M-expressing adenovirus (rAd/IL-12M) in mice bearing both solid and metastatic tumors.
383	21228885	Subcutaneous (s.c.) injection of MSCs/IL-12M at contralateral site of tumor exhibited similar levels of serum IL-12 and IFN-γ as i.t. injection, but much weaker antitumor effects in both B16F10 melanoma and TC-1 cervical cancer models than i.t. injection.
384	21321245	The current study demonstrated that a protocol to immunize the C57BL/6 mice with OK-432 followed by treatment with TC-1 lysate can generate markedly increased immune responses of E7-specific CD4(+) T cells and a moderate increase of natural killer (NK) cell, as well as a satisfactorily protective and therapeutic antitumor effect by triggering the DCs to prime T cells.
385	21321245	Depletion of lymphocyte subset in vivo suggested that the antitumor effects could be dominantly executed by CD8+ T cells and followed by NK cells, and both of these reactions were induced by the generation of robust E7-specific CD4(+) T helper cell response.
386	21722685	Immunization of protein HPV16 E7 in fusion with mouse HSP70 inhibits the growth of TC-1 cells in tumor bearing mice.
387	22008913	However, the VV.mIFNβ vector was able to augment the efficacy of an antitumor vaccine in the TC-1 tumor model in association with increased numbers of infiltrating CD8 T-cells.
388	22095092	In the present study, we demonstrate that CAF01/poly(I:C), termed cationic adjuvant formulation 05 or CAF05, can induce CD8(+) T cells that efficiently lyse target cells and significantly reduce tumor growth in two different mouse tumor models: lung B16-OVA melanoma expressing ovalbumin and the self-antigen TRP2, and subcutaneous TC-1 tumors expressing the human papillomavirus-16 protein E7.
389	22326819	Results showed that lymphocyte proliferation and some cytokines were significantly elevated, with cellular immune responses skewed towards Th1 and Tc1.
390	22509395	Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced anti-tumor effects.
391	22509395	Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we reason that a chimeric protein consisting of NKG2D linked to IL-2 will lead to the specific targeting of IL-2 to the tumor location.
392	22509395	Therefore, we created chimeric proteins consisting of NKG2D linked to Gaussia luciferase (GLuc; a marker protein) or IL-2 to form NKG2D-Fc-GLuc and NKG2D-Fc-IL2, respectively.
393	22509395	Furthermore, we showed that TC-1 tumor-bearing mice intramuscularly injected with DNA encoding NKG2D-Fc-IL2, followed by electroporation, exhibited an increased number of luciferase-expressing E7-specific CD8+ T cells at the tumor location.
394	22509395	Therefore, by linking NKG2D to IL2, we are able to specifically deliver IL-2 to the tumor location, enhancing antigen-specific T-cell immune response and controlling tumor growth.
395	22679502	Typhi antigens in T memory subsets, we developed multiparametric flow cytometry methods to detect up to 6 cytokines/chemokines (IL-10, IL-17A, IL-2, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein-1β (MIP-1β)) simultaneously.
396	22679502	Virtually all of the IL-17A detected was derived from multifunctional CD8+ T cells.
397	22679502	The presence of these multifunctional IL-17A+ CD8+ T cells was confirmed using an unsupervised analysis program, flow cytometry clustering without K (FLOCK).
398	22679502	The presence of IL-17A in multifunctional cells co-producing Tc1 cytokines (IL-2, IFN-γ and TNF-α) may also indicate that the distinction between Tc17 and Tc1 responses in humans is not as clearly delineated as suggested by in vitro experiments and animal models.
399	22926003	In the present study, three strategies including linkage to immunostimulatory molecules (N-terminal of gp96), co-administration of chemokines (IP-10 or RANTES) and PEI600-Tat as non-viral gene delivery system have been applied to enhance DNA vaccine efficacy against HPV infections.
400	22926003	Our results showed that co-administration of IP-10 with E7-NT-gp96 delivered by PEI600-Tat elicits significant IFN-γ production and consequently a strong preventive response against TC-1 tumor cells in contrast to increased tumor growth by RANTES co-delivery.
401	22926003	Also in therapeutic experiment, our data showed that co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivery by PEI600-Tat is able to significantly suppress TC-1 tumor growth.
402	22926003	In the present study, three strategies including linkage to immunostimulatory molecules (N-terminal of gp96), co-administration of chemokines (IP-10 or RANTES) and PEI600-Tat as non-viral gene delivery system have been applied to enhance DNA vaccine efficacy against HPV infections.
403	22926003	Our results showed that co-administration of IP-10 with E7-NT-gp96 delivered by PEI600-Tat elicits significant IFN-γ production and consequently a strong preventive response against TC-1 tumor cells in contrast to increased tumor growth by RANTES co-delivery.
404	22926003	Also in therapeutic experiment, our data showed that co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivery by PEI600-Tat is able to significantly suppress TC-1 tumor growth.
405	23162749	We conclude that the efficacy of Listeria-based vaccine does not rely on γδ T cells (or IL-17 produced by them) in a TC.1 tumor model; however, Listeria-based immunotherapy can be used to induce IL-17+ γδ T cells that are important for regression observed in alternative cancer models.
406	23377669	A major challenge associated with allogeneic hematopoietic stem cell transplantation is effective prevention and/or attenuation of symptoms associated with acute graft-versus-host disease (aGVHD) that can result from a failure of either host and/or donor CD4(+)CD25(+) regulatory T (Tr) and CD8(+)CD28 suppressor T (Ts) cells to dampen immunopathogenic responses mediated by alloreactive donor CD4(+)CD28(+) Th1 (Th1) and CD8(+)CD28(-) Tc1 (Tc1) cell-mediated inflammatory processes.
407	23377669	In addition, immunized mice presented with significantly diminished Th1-cytokines interferon-γ and interleukin-2 response and a moderately upregulated Th2-cytokine interleukin-10 and Th3-cytokine transforming growth factor-β response.
408	23428347	In this study, we explored the effects of a combination treatment consisting of a proteasome inhibitor, bortezomib, and an antigen specific STAT3-ablated (STAT3⁻/⁻) DC-based vaccine on the control of TC-1(P3) tumors, a p53-degraded immune resistant cancer cells.
409	23428347	We found that E7-antigen expressing STAT3⁻/⁻ DC (E7-DC-1STAT3⁻/⁻) vaccination enhanced generation of E7-specific CD8⁺ T cells, but was not enough to control TC-1(P3) cancer cells.
410	23428347	We found that apoptosis via down-regulation of STAT3 and NF-κB and up-regulation of Fas and death receptor 5 (DR5) expression in TC-1(P3) induced by bortezomib was independent of p53 status.
411	23428347	We also observed that TC-1(P3) cells pretreated with bortezomib had markedly enhanced anti-tumor effects on E7-specific CD8⁺ T cells through a Fas/DR5-mediated mechanism.
412	23428347	These results suggest that the anti-tumor effects against a p53-degraded immune resistant variant generated by antigen-expressing STAT3-ablated mature DCs may be enhanced by bortezomib via death receptor-mediated apoptosis.
413	23428347	In this study, we explored the effects of a combination treatment consisting of a proteasome inhibitor, bortezomib, and an antigen specific STAT3-ablated (STAT3⁻/⁻) DC-based vaccine on the control of TC-1(P3) tumors, a p53-degraded immune resistant cancer cells.
414	23428347	We found that E7-antigen expressing STAT3⁻/⁻ DC (E7-DC-1STAT3⁻/⁻) vaccination enhanced generation of E7-specific CD8⁺ T cells, but was not enough to control TC-1(P3) cancer cells.
415	23428347	We found that apoptosis via down-regulation of STAT3 and NF-κB and up-regulation of Fas and death receptor 5 (DR5) expression in TC-1(P3) induced by bortezomib was independent of p53 status.
416	23428347	We also observed that TC-1(P3) cells pretreated with bortezomib had markedly enhanced anti-tumor effects on E7-specific CD8⁺ T cells through a Fas/DR5-mediated mechanism.
417	23428347	These results suggest that the anti-tumor effects against a p53-degraded immune resistant variant generated by antigen-expressing STAT3-ablated mature DCs may be enhanced by bortezomib via death receptor-mediated apoptosis.
418	23428347	In this study, we explored the effects of a combination treatment consisting of a proteasome inhibitor, bortezomib, and an antigen specific STAT3-ablated (STAT3⁻/⁻) DC-based vaccine on the control of TC-1(P3) tumors, a p53-degraded immune resistant cancer cells.
419	23428347	We found that E7-antigen expressing STAT3⁻/⁻ DC (E7-DC-1STAT3⁻/⁻) vaccination enhanced generation of E7-specific CD8⁺ T cells, but was not enough to control TC-1(P3) cancer cells.
420	23428347	We found that apoptosis via down-regulation of STAT3 and NF-κB and up-regulation of Fas and death receptor 5 (DR5) expression in TC-1(P3) induced by bortezomib was independent of p53 status.
421	23428347	We also observed that TC-1(P3) cells pretreated with bortezomib had markedly enhanced anti-tumor effects on E7-specific CD8⁺ T cells through a Fas/DR5-mediated mechanism.
422	23428347	These results suggest that the anti-tumor effects against a p53-degraded immune resistant variant generated by antigen-expressing STAT3-ablated mature DCs may be enhanced by bortezomib via death receptor-mediated apoptosis.
423	23428347	In this study, we explored the effects of a combination treatment consisting of a proteasome inhibitor, bortezomib, and an antigen specific STAT3-ablated (STAT3⁻/⁻) DC-based vaccine on the control of TC-1(P3) tumors, a p53-degraded immune resistant cancer cells.
424	23428347	We found that E7-antigen expressing STAT3⁻/⁻ DC (E7-DC-1STAT3⁻/⁻) vaccination enhanced generation of E7-specific CD8⁺ T cells, but was not enough to control TC-1(P3) cancer cells.
425	23428347	We found that apoptosis via down-regulation of STAT3 and NF-κB and up-regulation of Fas and death receptor 5 (DR5) expression in TC-1(P3) induced by bortezomib was independent of p53 status.
426	23428347	We also observed that TC-1(P3) cells pretreated with bortezomib had markedly enhanced anti-tumor effects on E7-specific CD8⁺ T cells through a Fas/DR5-mediated mechanism.
427	23428347	These results suggest that the anti-tumor effects against a p53-degraded immune resistant variant generated by antigen-expressing STAT3-ablated mature DCs may be enhanced by bortezomib via death receptor-mediated apoptosis.
428	23521528	We have engineered a nononcogenic mutated E7-specific plasmo-retroVLP vaccine (pVLP-E7), consisting of plasmid DNA, that is able to form recombinant retrovirus-based virus-like particles (VLPs) that display E7 antigen into murine leukemia virus Gag proteins pseudotyped with vesicular stomatitis virus envelope glycoprotein (VSV-G). pVLP-E7 vaccinations were studied for their ability to generate specific immune responses and for induction of protective immunity against tumor cell challenge in preventive and therapeutic models.
429	23521528	Intradermic vaccinations of mice with pVLP-E7 show their efficacy to generate antigen-specific T cell responses, to prevent and protect animals from early TC-1 tumor development compared with standard DNA or VLP immunizations.
430	23521528	Data show that pVLP-E7 vaccination can cure mice with already established tumors only when combined with Toll-like receptor-7 (TLR7) and TLR9 agonists.
431	23615841	We found that TC-1 tumor-bearing C57BL/6 mice treated with cisplatin and intratumoral injection of CRT/E7-VV significantly increased E7-specific CD8+ T cells in the blood and generated potent local and systemic antitumor immune responses compared to mice receiving cisplatin and CRT/E7-VV intraperitoneally or mice treated with cisplatin alone.
432	23799135	The E6-RHDV-VLP-PADRE was administered therapeutically for the treatment of a pre-existing TC-1 tumour and was delivered with antibodies either to deplete regulatory T cells (anti-CD25) or to block T cell suppression mediated through CTLA-4.
433	23831323	We noticed that TC-1 cells do not express Toll-like receptor 5 (TLR5) on their surface and the TLR5 signaling pathway in TC-1 cells was not responsible for the antitumor effect of FlaB.
434	23831323	In addition, this antitumor activity was abrogated following the in vivo depletion of CD8(+) T cells and in TLR5 knockout (KO) or MyD88 KO mice.
435	23831323	These results suggest that flagellin could enhance TA-specific CD8(+) CTL immune responses through TLR5 stimulation in cancer immunotherapy.
436	23839107	Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore.
437	23839107	Vaccination induced YF-17D-NS3-specific CD8/IFNγ responses, without significant TNFα, and a CYD-specific Th1/Tc1 cellular response in all participants, which was characterized by predominant IFNγ secretion compared with TNFα, associated with low level IL-13 secretion in multiplex analysis of peripheral blood mononuclear cells (PBMC) supernatants after restimulation with each the CYD vaccine viruses.
438	23877655	BM-derived DCs infected by ad-shRNA-SOCS1 were pulsed with the HPV16mE7 protein and then were transfused into mouse models bearing TC-1 tumor cells expressing HPV16 E6/E7.
439	23877655	IFN-γ, cytokine (TNF-α, IL-12, IL-6) expression, anti-E7 antibody and cytotoxic T lymphocyte (CTL) levels were measured.
440	24066030	We herein investigated this issue using two vaccine formulations containing a novel costimulatory molecule, SA-4-1BBL, as adjuvant and HPV E7 or survivin (SVN) as tumor associated antigens (TAAs) in two mouse transplantable tumor models; the TC-1 cervical cancer expressing xenogeneic HPV E7 and 3LL lung carcinoma overexpressing autologous SVN.
441	24066030	The in vivo depletion of CD4(+) T cells one day before tumor challenge resulted in compromised vaccine efficacy in both TC-1 (25%) and 3LL (12.5%) tumor models.
442	24066030	Collectively, these results demonstrate the indispensable role CD4(+) T cells play in the generation of therapeutic primary immune responses elicited by SA-4-1BBL/TAA-based vaccines irrespective of the nature of TAAs and establish the importance of CD4(+) T cells for long-term immune memory against 3LL tumor expressing self-antigen SVN, but not TC-1 expressing xenogeneic viral antigen E7.
443	24066030	We herein investigated this issue using two vaccine formulations containing a novel costimulatory molecule, SA-4-1BBL, as adjuvant and HPV E7 or survivin (SVN) as tumor associated antigens (TAAs) in two mouse transplantable tumor models; the TC-1 cervical cancer expressing xenogeneic HPV E7 and 3LL lung carcinoma overexpressing autologous SVN.
444	24066030	The in vivo depletion of CD4(+) T cells one day before tumor challenge resulted in compromised vaccine efficacy in both TC-1 (25%) and 3LL (12.5%) tumor models.
445	24066030	Collectively, these results demonstrate the indispensable role CD4(+) T cells play in the generation of therapeutic primary immune responses elicited by SA-4-1BBL/TAA-based vaccines irrespective of the nature of TAAs and establish the importance of CD4(+) T cells for long-term immune memory against 3LL tumor expressing self-antigen SVN, but not TC-1 expressing xenogeneic viral antigen E7.
446	24066030	We herein investigated this issue using two vaccine formulations containing a novel costimulatory molecule, SA-4-1BBL, as adjuvant and HPV E7 or survivin (SVN) as tumor associated antigens (TAAs) in two mouse transplantable tumor models; the TC-1 cervical cancer expressing xenogeneic HPV E7 and 3LL lung carcinoma overexpressing autologous SVN.
447	24066030	The in vivo depletion of CD4(+) T cells one day before tumor challenge resulted in compromised vaccine efficacy in both TC-1 (25%) and 3LL (12.5%) tumor models.
448	24066030	Collectively, these results demonstrate the indispensable role CD4(+) T cells play in the generation of therapeutic primary immune responses elicited by SA-4-1BBL/TAA-based vaccines irrespective of the nature of TAAs and establish the importance of CD4(+) T cells for long-term immune memory against 3LL tumor expressing self-antigen SVN, but not TC-1 expressing xenogeneic viral antigen E7.
449	24083082	Here, we report that the administration of L. monocytogenes-based anticancer vaccines increases the secretion of chemokine (C-X-C motif) ligand 9 (CXCL9), and CXCL10 by tumors, hence favoring the recruitment of T cells bearing the cognate chemokine (C-X-C motif) receptor 3 (CXCR3).
450	24083082	Furthermore, the expression of CXCL9, but not CXCL10, in TC-1 tumors was significantly reduced upon anti-IFNγ antibody treatment.
451	24083082	CXCL9 was highly expressed by TC-1 cells following the administration of IFNγ and tumor necrosis factor α (TNFα), in vitro.
452	24083082	Moreover, the inhibition of CXCL9 in TC-1 cells reduced the proportion of CD8⁺ T cells infiltrating tumors in vaccinated mice, while increasing that of CD4⁺ T cells, thus altering T-cell subset distribution.
453	24083082	Here, we report that the administration of L. monocytogenes-based anticancer vaccines increases the secretion of chemokine (C-X-C motif) ligand 9 (CXCL9), and CXCL10 by tumors, hence favoring the recruitment of T cells bearing the cognate chemokine (C-X-C motif) receptor 3 (CXCR3).
454	24083082	Furthermore, the expression of CXCL9, but not CXCL10, in TC-1 tumors was significantly reduced upon anti-IFNγ antibody treatment.
455	24083082	CXCL9 was highly expressed by TC-1 cells following the administration of IFNγ and tumor necrosis factor α (TNFα), in vitro.
456	24083082	Moreover, the inhibition of CXCL9 in TC-1 cells reduced the proportion of CD8⁺ T cells infiltrating tumors in vaccinated mice, while increasing that of CD4⁺ T cells, thus altering T-cell subset distribution.
457	24083082	Here, we report that the administration of L. monocytogenes-based anticancer vaccines increases the secretion of chemokine (C-X-C motif) ligand 9 (CXCL9), and CXCL10 by tumors, hence favoring the recruitment of T cells bearing the cognate chemokine (C-X-C motif) receptor 3 (CXCR3).
458	24083082	Furthermore, the expression of CXCL9, but not CXCL10, in TC-1 tumors was significantly reduced upon anti-IFNγ antibody treatment.
459	24083082	CXCL9 was highly expressed by TC-1 cells following the administration of IFNγ and tumor necrosis factor α (TNFα), in vitro.
460	24083082	Moreover, the inhibition of CXCL9 in TC-1 cells reduced the proportion of CD8⁺ T cells infiltrating tumors in vaccinated mice, while increasing that of CD4⁺ T cells, thus altering T-cell subset distribution.
461	24296809	Most importantly, DCs matured with OK-432 plus IFN-γ-induced maintained secretion of interleukin-12 (IL-12)p70 in secondary culture after stimulus withdrawal.
462	24296809	Functionally, OK-432 plus IFN-γ-conditioned DCs induce remarkable Th1 and Tc1 responses more effectively than OK-432 alone, even more than the use of α-type-1 cytokine cocktail.
463	24396491	The present study evaluated the protective effects of intranasally administered live L. lactis strains carrying human papillomavirus 16 E7 protein and murine interleukin-12 (IL-12) DNA (LL-E7_P-IL-12_D) in a TC-1 tumor animal model.
464	24396491	IL-12 and interferon-γ serum levels were measured and immunization with LL-E7_P-IL-12_D was shown to induce an E7-specific immune response and to confer protection against TC-1-induced tumors in vivo.
465	24396491	The present study evaluated the protective effects of intranasally administered live L. lactis strains carrying human papillomavirus 16 E7 protein and murine interleukin-12 (IL-12) DNA (LL-E7_P-IL-12_D) in a TC-1 tumor animal model.
466	24396491	IL-12 and interferon-γ serum levels were measured and immunization with LL-E7_P-IL-12_D was shown to induce an E7-specific immune response and to confer protection against TC-1-induced tumors in vivo.
467	24728077	PD-1/B7-H1 is an important inhibitory axis in the tumor microenvironment.
468	24728077	We observed that using anti-PD-1 antibody and a multipeptide vaccine (consisting of immunogenic peptides derived from breast cancer antigens, neu, legumain, and β-catenin) as a combination therapy regimen for the treatment of breast cancer-bearing mice prolonged the vaccine-induced progression-free survival period.
469	24728077	This prolonged survival was associated with increase in number of Tc1 and Tc2 CD8 T cells with memory precursor phenotype, CD27+IL-7RhiT-betlo, and decrease in number of PD-1+ dendritic cells (DC) in regressing tumors and enhanced antigen reactivity of tumor-infiltrating CD8 T cells.
470	24728077	It was also observed that blockade of PD-1 on tumor DCs enhanced IL-7R expression on CD8 T cells.
471	24728077	Taken together, our results suggest that PD-1 blockade enhances breast cancer vaccine efficacy by altering both CD8 T cell and DC components of the tumor microenvironment.
472	24789529	The Sox2 gene was codon optimized for the expression in human cells, its sequences encoding two nuclear localization signals (NLSs) were mutagenized, and the sequence coding for the PADRE helper epitope was fused with its 5' terminus.
473	24789529	The antitumor effect was shown after immunization against mouse oncogenic TC-1/B7 cells derived from the lung cancer cell line TC-1 and characterized by high Sox2 production.
474	24983823	IL-10 signalling blockade at the time of immunization inhibits Human papillomavirus 16 E7 transformed TC-1 tumour cells growth in mice.
475	24983823	IL-10 signalling blockade by intra-peritoneal injection of anti-IL-10 receptor antibodies at the time of immunization enhances vaccine induced CD8+ T cell responses and promotes bacteria, parasitic and viral control.
476	24983823	We now show that blockade of IL-10 signalling at the time of immunization enhances vaccine induced antigen specific CD8+ T cell responses to both dominant and subdominant CTL epitopes.
477	24983823	Injection of anti-IL-10 receptor antibodies subcutaneous at the time of immunization also enhances CD8+ T cell responses.
478	24983823	Furthermore, IL-10 signalling blockade at the time of a Human papillomavirus 16 E7 peptide/LPS immunization, prevents HPV16 E7 transformed TC-1 tumour growth in mice.
479	24983823	IL-10 signalling blockade at the time of immunization inhibits Human papillomavirus 16 E7 transformed TC-1 tumour cells growth in mice.
480	24983823	IL-10 signalling blockade by intra-peritoneal injection of anti-IL-10 receptor antibodies at the time of immunization enhances vaccine induced CD8+ T cell responses and promotes bacteria, parasitic and viral control.
481	24983823	We now show that blockade of IL-10 signalling at the time of immunization enhances vaccine induced antigen specific CD8+ T cell responses to both dominant and subdominant CTL epitopes.
482	24983823	Injection of anti-IL-10 receptor antibodies subcutaneous at the time of immunization also enhances CD8+ T cell responses.
483	24983823	Furthermore, IL-10 signalling blockade at the time of a Human papillomavirus 16 E7 peptide/LPS immunization, prevents HPV16 E7 transformed TC-1 tumour growth in mice.
484	24990079	The HspX protein induces DC maturation and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IFN-β) through TLR4 binding partially mediated by both the MyD88 and the TRIF signaling pathways.
485	24990079	The administration of HspX-stimulated DCs increased the activation of naive T cells, effectively polarizing the CD4(+) and CD8(+) T cells to secrete IFN-γ, as well as enhanced the cytotoxicity of splenocytes against HPV-16 E7 (E7)-expressing TC-1 murine tumor cells in therapeutic experimental animals.
486	25153350	Our previous study demonstrated that the extracellular domain of murine BTLA (the soluble form of BTLA) can facilitate HSP70 vaccine-triggered antitumor immunity by blocking BTLA-HVEM interactions in a murine TC-1 non-metastatic tumor model.
487	25153350	Furthermore, the Th1 cytokines IL-2 and IFN-γ were up-regulated, while the negative regulatory molecules IL-10 and TGF-β were down-regulated.
488	25265018	To improve anti-tumor effects of therapeutic vaccine, we fused cytotoxic T-lymphocyte antigen 4 (CTLA-4) with HPV16 E7 and E6 as a fusion therapeutic DNA vaccine (pCTLA4-E7E6). pCTLA4-E7E6 induced significantly higher anti-E7E6 specific antibodies and relatively stronger specific CTL responses than the nonfusion DNA vaccine pE7E6 in C57BL/6 mice bearing with TC-1 tumors. pCTLA4-E7E6 showed relatively stronger anti-tumor effects than pE7E6 in therapeutic immunization.
489	25499555	When the conjugate was treated with CD44(high) TC-1 tumor cells, it was effectively taken up and allowed for displaying of antigenic OVA257-264 peptide at MHC class I on the surface of the cells.
490	25530186	A direct comparison to Poly(I:C) showed superior efficacy of our adjuvant to enhance antigen-specific multifunctional CD8(+) T-cell responses and mediate anti-tumor responses induced by peptide derived from HPV-16 E7 protein in the syngeneic TC-1 tumor, a murine model of human HPV-induced cervical cancer.
491	25701675	Local administration of granulocyte macrophage colony-stimulating factor induces local accumulation of dendritic cells and antigen-specific CD8+ T cells and enhances dendritic cell cross-presentation.
492	25701675	Granulocyte macrophage colony-stimulating factor (GMCSF) has been reported to posses the ability to induce migration of antigen presentation cells and CD8+ T cells.
493	25701675	Therefore, in the current study, we employ a combination of systemic therapeutic HPV DNA vaccination with local GMCSF application in the TC-1 tumor model.
494	25701675	We show that intramuscular vaccination with CRT/E7 DNA followed by GMCSF intravaginal administration effectively controls cervicovaginal TC-1 tumors in mice.
495	25701675	Local administration of granulocyte macrophage colony-stimulating factor induces local accumulation of dendritic cells and antigen-specific CD8+ T cells and enhances dendritic cell cross-presentation.
496	25701675	Granulocyte macrophage colony-stimulating factor (GMCSF) has been reported to posses the ability to induce migration of antigen presentation cells and CD8+ T cells.
497	25701675	Therefore, in the current study, we employ a combination of systemic therapeutic HPV DNA vaccination with local GMCSF application in the TC-1 tumor model.
498	25701675	We show that intramuscular vaccination with CRT/E7 DNA followed by GMCSF intravaginal administration effectively controls cervicovaginal TC-1 tumors in mice.
499	25753156	The siRNA cocktail targeting interleukin 10 receptor and transforming growth factor-β receptor on dendritic cells potentiates tumour antigen-specific CD8(+) T cell immunity.
500	25753156	The potency of DCs, however, is readily attenuated immediately after their administration in patients as tumours and various immune cells, including DCs, produce various immunosuppressive factors such as interleukin (IL)-10 and transforming growth factor (TGF)-β that hamper the function of DCs.
501	25753156	Among the siRNAs targeting various immunosuppressive molecules, we observed that DCs transfected with siRNA targeting IL-10 receptor alpha (siIL-10RA) initiated the strongest antigen-specific CD8(+) T cell immune responses.
502	25753156	The potency of siIL-10RA was enhanced further by combining it with siRNA targeting TGF-β receptor (siTGF-βR), which was the next best option during the screening of this study, or the previously selected immunoadjuvant siRNA targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN) or Bcl-2-like protein 11 (BIM).
503	25753156	Concordantly, the knock-down of both IL-10RA and TGF-βR in DCs induced the strongest anti-tumour effects in the TC-1 P0 tumour model, a cervical cancer model expressing the human papillomavirus (HPV)-16 E7 antigen, and even in the immune-resistant TC-1 (P3) tumour model that secretes more IL-10 and TGF-β than the parental tumour cells (TC-1 P0).
504	26122844	In animals vaccinated with CyaA-E7, rapamycin administration completely abolished recruitment of CD8+ T cells into TC-1 tumors along with the ability of the vaccine to reduce infiltration of T regulatory cells and myeloid-derived suppressor cells.
505	26289530	Interestingly, XHL in conjunction with inactivated FMD vaccine activated strong Th1 and Tc1 cell responses, especially Tfh cell responses, in immunized mice.
506	26289530	XHL stimulated dendritic cell maturation by upregulating expression of major histocompatibility complex II (MHCII) molecules and co-stimulatory molecules CD40 and CD86 in immunized mice.
507	26336989	Furthermore, vaccination with PAUF treated DCs pulsed with E7 or OVA peptides leads to generation of E7 or OVA-specific CD8+ T cells and memory T cells, which correlate with long term tumor protection and antitumor effects against TC-1 and EG.7 tumors in mice.
508	26351680	Antibody modulation of T-cell coinhibitory (e.g., CTLA-4) or costimulatory (e.g., 4-1BB) receptors promotes clinical responses to a variety of cancers.
509	26351680	Combining this E6/E7 peptide vaccine with checkpoint blockade produced only modest benefit; however, coadministration with a 4-1BB agonist antibody promoted durable regression of established genital TC-1 tumors.
510	26351680	Relative to other therapies tested, this combination of vaccine and α4-1BB promoted the highest CD8(+) versus regulatory FoxP3(+) T-cell ratios, elicited 2- to 5-fold higher infiltration by E7-specific CTL, and evoked higher densities of highly cytotoxic TcEO (T cytotoxic Eomesodermin) CD8 (>70-fold) and ThEO (T helper Eomesodermin) CD4 (>17-fold) T cells.
511	26390407	Tumor preventive assays, based on the engraftment of TC-1 cells in mice, showed that the E6E7 multi-epitope protein induced a full preventive anti-tumor protection in wild-type mice, as well as in mice deficient in expression of CD4+ T cells and TLR4 receptor.