title: Clinical Activity, Toxicity, Biomarkers, and Future Development of CTLA-4 Checkpoint Antagonists.
abstract: Evidence that the immune system can recognize, and in some cases control or even eliminate tumors, is increasingly clear. Encouraging T-cell activation by blocking regulatory or "checkpoint" molecules is a potent way to amplify anti-tumor immune responses. Successfully exploiting this concept, a new class of anti-cancer therapies, "checkpoint-blocking" antibodies has emerged. The first checkpoint-blocking antibody to enter the clinic was ipilimumab, an antibody that blocks the co-inhibitory receptor cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Herein we review the clinical development of CTLA-4 blocking antibodies, including preclinical studies, clinical activity, toxicities, the search for potential biomarkers, and early clinical experience with combinations.
authors: Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; Weill Medical College of Cornell University, New York, NY. Electronic address: callahan@mskcc.org.
authors: Margaret K
authors: MK
authors: Callahan
authors: Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; Weill Medical College of Cornell University, New York, NY; Ludwig Center for Cancer Immunotherapy, New York, NY.
authors: Jedd D
authors: JD
authors: Wolchok
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D006801:Humans; D000074324:Ipilimumab; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D060908:CTLA-4 Antigen; D000074324:Ipilimumab