Synergistic antitumor effect of chemotactic-prostate tumor-associated antigen gene-modified tumor cell vaccine and anti-CTLA-4 mAb in murine tumor model.
In this study, we demonstrate that an effective immune response against prostate tumors in mouse tumor model can be elicited using a strategy that combines CTLA-4 blockade and pSLC-3P-Fc-modified tumor cell vaccine (named B16F10-SLC-3P-Fc). Treatment of B16F10-3P-bearing mice resulted in a significant reduction in tumor incidence as assessed 2 months after treatment. In vivo Ab depletion confirmed that the antitumor effect was primarily CD8+ T cells and CD4+ T lymphocytes were required for the induction of CD8+ CTL response in B16F10-SLC-3P-Fc+anti-CTLA-4 mAb-immunized mice. Moreover, mice that were cured of an established tumor were protected against a rechallenge with the same tumor for at least 4 months, suggesting the generation of memory responses. Adoptive transfer experiments further indicate that antitumor reactivity can be transferred to naïve mice by splenocytes. These findings demonstrate that this combinatorial treatment can elicit a potent anti-tumor immune response and suggest potential of this approach for treatment of prostate cancer.
Li
Ning
N
Department of Immunology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Qin
Hanjun
H
Li
Xiaozhu
X
Zhou
Chunxia
C
Wang
Dongmei
D
Ma
Wenbo
W
Lin
Chen
C
Zhang
Youhui
Y
Wang
Shengdian
S
Zhang
Shuren
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011467:Prostate / Q000276:immunology; D017430:Prostate-Specific Antigen / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; C556707:Ctla4 protein, mouse; D017430:Prostate-Specific Antigen