title: The evolution of checkpoint blockade as a cancer therapy: what's here, what's next?
abstract: Unleashing the immune system to fight cancer has become one of the main treatment modalities since the anti-CTLA-4 antibody, ipilimumab was approved for patients with advanced melanoma in 2011. Pembrolizumab and nivolumab, two anti-PD-1 antibodies recently approved for the treatment of patients with metastatic melanoma, are being actively investigated for the treatment of multiple caners including lung, breast, bladder and renal cancers along with other anti-PD-1/L1 antibodies. Early results of combining of anti-CTLA-4 antibody and anti-PD-1 antibody treatment for advanced melanoma patients are showing impressive response rates with manageable toxicity profiles. There are several other checkpoint molecules that are likely potential inhibitory targets. The outcome of blocking some of these negative immune regulators, such as LAG-3 or TIM-3, is being pursued in the clinic or about to enter clinical development. Blockade of these molecules is demonstrating promising preclinical activity alone or when combined with anti-PD-1/L1. Future studies will define bio-markers of these therapies and how to target them alone or in combination with other immunotherapies, chemotherapy, radiotherapy and small molecule inhibitors.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), Los Angeles, CA, USA; Department of Molecular, Cellular and Integrative Physiology, UCLA, Los Angeles, CA, USA.
authors.forename: Daniel Sanghoon
authors.initials: DS
authors.lastname: Shin
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USA; Department of Surgery, Division of Surgical-Oncology, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-1782, USA; Department of Molecular, Cellular and Integrative Physiology, UCLA, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu.
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000037:antagonists & inhibitors; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D060908:CTLA-4 Antigen; D061025:Costimulatory and Inhibitory T-Cell Receptors; D061026:Programmed Cell Death 1 Receptor