CTLA-4: new insights into its biological function and use in tumor immunotherapy.
The discovery of multiple costimulatory cell surface molecules that influence the course of T cell activation has increased our appreciation of the complexity of the T cell response. It remains clear, however, that CD28 and cytotoxic T lymphocyte antigen 4 (CTLA-4) are the critical costimulatory receptors that determine the early outcome of stimulation through the T cell antigen receptor (TCR). Details of how the T cell integrates TCR stimulation with the costimulatory signals of CD28 and the inhibitory signals of CTLA-4 remain to be established, but unique features of the cell biology of CTLA-4 provide important insights into its function. We summarize here recent findings that suggest a previously unrecognized role for CTLA-4 in the regulation of T cell responses. We also describe preclinical and clinical results that indicate manipulation of CTLA-4 has considerable promise as a strategy for the immunotherapy of cancer.
Egen
Jackson G
JG
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720, USA.
Kuhns
Michael S
MS
Allison
James P
JP
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D060908:CTLA-4 Antigen; D002455:Cell Division; D003110:Colonic Neoplasms / Q000628:therapy; D004195:Disease Models, Animal; D005354:Fibrosarcoma / Q000628:therapy; D005786:Gene Expression Regulation; D006801:Humans; D018796:Immunoconjugates; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D000069594:Abatacept