title: Immune modulation in cancer with antibodies.
abstract: Ipilimumab is the prototypical immunomodulatory antibody, approved by the FDA in 2011 for advanced melanoma on the basis of survival benefit. Since that time, we have made significant strides in optimizing this therapy: we have characterized the spectrum of immune-related adverse events and learned how to mitigate them with treatment algorithms, discovered potential biomarkers of activity, and identified the potential synergy between checkpoint modulation and other therapeutic modalities. Recent phase I trials have established the efficacy and safety of next-generation checkpoint agents, including PD-1 and PD-L1 inhibitors, across multiple tumor types. Much work lies ahead in developing these next-generation checkpoint agents, testing them in combination, and determining how to integrate them into the treatment paradigms of various tumor types.
authors.affiliation: Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York 10065; email: paged@mskcc.org , postowm@mskcc.org , callaham@mskcc.org , wolchokj@mskcc.org.
authors.forename: David B
authors.initials: DB
authors.lastname: Page
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Callahan
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; D007155:Immunologic Factors; D000074324:Ipilimumab; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C520704:tremelimumab