B7 blockade alters the balance between regulatory T cells and tumor-reactive T cells for immunotherapy of cancer.
OBJECTIVE
In prostate cancer-bearing host, regulatory T (Treg) cells restrain activity of tumor antigen-specific T cells. Because B7:CD28 interactions are needed for both function of CD4+CD25+ Treg cells and CD8+ effective T cells, targeting this pathway may help to overcome the immunotherapy barriers.


METHODS
The anti-B7-1/B7-2 monoclonal antibodies were administered to a transgenic mouse model of prostate cancer (TRAMP) ectopically expressing SV40 large T antigen in different tumor development stages for prevention and therapy of prostate cancer. The treatment was also tested in treating transplanted MC38 colon adenocarcinoma in mice.


RESULTS
Here, we showed that short-term administration of anti-B7-1/B7-2 monoclonal antibodies in TRAMP mice leads to significant inhibited primary tumor growth and the size of metastatic lesions. The treatment is effective to inhibit MC38 colon cancer growth. Correspondingly, this treatment results in a transient reduction of Treg in both thymus and the periphery. In vivo cytotoxicity assay revealed T antigen-specific CTL effectors in anti-B7-treated but not control IgG-treated TRAMP mice.


CONCLUSIONS
Transient blockade of B7-1/B7-2 alters the balance between Treg and cancer-reactive T cells to enhance cancer immunotherapy.
Zhou
Penghui
P
Department of Surgery and Pathology, University of Michigan Medical Center, Program of Molecular Mechanism of Diseases and Comprehensive Cancer Center, Ann Arbor, Michigan 48109, USA.
Zheng
Xincheng
X
Zhang
Huiming
H
Liu
Yang
Y
Zheng
Pan
P
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000494:pharmacology*; D051940:B7-2 Antigen / Q000494:pharmacology*; D004195:Disease Models, Animal; D007167:Immunotherapy / Q000379:methods; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C429108:107-1A4 monoclonal antibody; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D053645:Interleukin-2 Receptor alpha Subunit