Enhancement of antitumor immunity by CTLA-4 blockade

DR Leach, MF Krummel, JP Allison - Science, 1996 - science.org
DR Leach, MF Krummel, JP Allison
Science, 1996science.org
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 …
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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