Enhancement of antitumor immunity by CTLA-4 blockade.
One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. It has recently become apparent that CTLA-4, a second counterreceptor for the B7 family of costimulatory molecules, is a negative regulator of T cell activation. Here, in vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells.
Leach
D R
DR
Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.
Krummel
M F
MF
Allison
J P
JP
D000069594:Abatacept; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D060908:CTLA-4 Antigen; D005260:Female; D006084:Graft Rejection; D018796:Immunoconjugates; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D000069594:Abatacept