Role of anti-CTLA-4 therapies in the treatment of cancer.
Studies in the field of T-cell receptor (TCR)/antigen (Ag) recognition have led to the discovery of a unique receptor/ligand system that, in collaboration with TCR/Ag engagement, underlies the molecular basis of T-cell activation and proliferation. Such a process has been termed co-stimulation, which serves to either upregulate or downregulate T-cell signaling following TCR ligation. As neoplasia represents a pathogenic process whereby a sustained T-cell response may be desirable, intensive efforts to prolong endogenous tumor-induced T-cell activity in vivo have been investigated. One innovative approach has been to block a crucial inhibitory arm of the co-stimulatory pathway using monoclonal antibodies against the CTLA-4 molecule expressed by Ag-primed, activated T-cells. In both preclinical models and clinical settings, such a therapeutic intervention has been found to be effective in promoting antitumor T-cell responses and, in some patients, clinical regression has been concomitant with autoreactivity. Thus, CTLA-4 blockade, perhaps in conjunction with other oncological modalities, may comprise important therapeutic paradigms to facilitate long-lasting antineoplastic immunity.
Abrams
Scott I
SI
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 5846, Bethesda, MD 20892-1402, USA. sa47z@nih.gov
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D060908:CTLA-4 Antigen; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell