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Semin Oncol. 2015 Aug;42(4):573-86. doi: 10.1053/j.seminoncol.2015.05.008. Epub 2015 Jun 3.

Clinical Activity, Toxicity, Biomarkers, and Future Development of CTLA-4 Checkpoint Antagonists.

Author information

1
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.
2
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.

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.

[Indexed for MEDLINE]

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