title: Immune Checkpoint Blockade in Cancer Therapy.
abstract: Immunologic checkpoint blockade with antibodies that target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein 1 pathway (PD-1/PD-L1) have demonstrated promise in a variety of malignancies. Ipilimumab (CTLA-4) and pembrolizumab (PD-1) are approved by the US Food and Drug Administration for the treatment of advanced melanoma, and additional regulatory approvals are expected across the oncologic spectrum for a variety of other agents that target these pathways. Treatment with both CTLA-4 and PD-1/PD-L1 blockade is associated with a unique pattern of adverse events called immune-related adverse events, and occasionally, unusual kinetics of tumor response are seen. Combination approaches involving CTLA-4 and PD-1/PD-L1 blockade are being investigated to determine whether they enhance the efficacy of either approach alone. Principles learned during the development of CTLA-4 and PD-1/PD-L1 approaches will likely be used as new immunologic checkpoint blocking antibodies begin clinical investigation.
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Callahan
authors.affiliation: All authors: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY. wolchokj@mskcc.org.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D004334:Drug Administration Schedule; D006801:Humans; D000074324:Ipilimumab; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab