Enhancement of Antitumor Immunity by CTLA-4 Blockade
Dana R. Leach(University of California, Berkeley), Matthew F. Krummel(University of California, Berkeley), James P. Allison(University of California, Berkeley)
Cited by 3,908
Abstract
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.
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