title: At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy.
abstract: It is increasingly appreciated that cancers are recognized by the immune system, and under some circumstances, the immune system may control or even eliminate tumors. The modulation of signaling via coinhibitory or costimulatory receptors expressed on T cells has proven to be a potent way to amplify antitumor immune responses. This approach has been exploited successfully for the generation of a new class of anticancer therapies, "checkpoint-blocking" antibodies, exemplified by the recently FDA-approved agent, ipilimumab, an antibody that blocks the coinhibitory receptor CTLA-4. Capitalizing on the success of ipilimumab, agents that target a second coinhibitory receptor, PD-1, or its ligand, PD-L1, are in clinical development. Lessons learned from treating patients with CTLA-4 and PD-1 pathway-blocking antibodies will be reviewed, with a focus on concepts likely to inform the clinical development and application of agents in earlier stages of development. See related review At the bench: Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy.
authors.affiliation: Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10065, USA.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Callahan
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
mesh_terms: D019138:Antibodies, Blocking / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: endpoints; overall survival; tumor