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Enhancement of Antitumor Immunity by CTLA-4 Blockade

Dana R. Leach, Matthew F. Krummel, James P. Allison

1996Science3,921 citationsDOI

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.

Topics & Concepts

CTLA-4ImmunogenicityBlockadeCD28ImmunologyImmunityRegulatorImmune systemAntibodyCancer researchT cellBiologyMedicineReceptorInternal medicineGeneBiochemistryCancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesImmune Cell Function and Interaction