title: Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer.
abstract: Programmed cell death protein 1 (PD-1) and its ligands, programmed cell death 1 ligand 1 (PD-L1) and 2 (PD-L2) play an important role in regulating immune response through various mechanisms. This inhibitory action is thought to assist in immune evasion by cancer cells as PD-1, PD-L1 and PD-L2 have been found to be abnormally expressed by tumor cells and lymphocytes in the tumor microenvironment. Preclinical studies described PD-1 blockade resulting in tumor growth suppression and even decreased metastasis. This has led to the development of pembrolizumab (MK-3475), a highly selective, humanized monoclonal IgG4-kappa isotype antibody against PD-1. Early clinical trials have shown high tumor response rates and long duration of effect in previously treated advanced melanoma resulting in accelerated FDA approval for the drug in this situation. Pembrolizumab has also had success in non-small cell lung cancer and is being tested in multiple other tumor types. This review will discuss the development, preclinical data, pharmacokinetics and clinical efficacy to date of pembrolizumab.
authors: Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors: J
authors: J
authors: McDermott
authors: Developmental Therapeutics Program, University of Colorado School of Medicine, Aurora, Colorado, USA. Antonio.Jimeno@ucdenver.edu.
authors: A
authors: A
authors: Jimeno
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab
keywords: Anti-PD-1 antibody; Lambrolizumab; MK-3475; Melanoma; NSCLC; Pembrolizumab