title: [Anti-PD-1 antibody: basics and clinical application].
abstract: Although the treatment of cancer with monoclonal antibodies has long been pursued, T cell-directed immunotherapy has met with limited success. Recently, much attention has been devoted to the blockade of PD-1 signaling to activate an immune response to cancer. PD-1, a protein expressed on T cells, is a member of the CD28 superfamily, and it transmits coinhibitory signals upon engagement with its ligands PD-L1 and PD-L2. Accumulating evidence suggests that the PD-1 system plays pivotal roles in the regulation of autoimmunity, transplantation immunity, infectious immunity, and tumor immunity. Because the interaction of PD-1 with its ligands occurs in the effector phase of killer T cell responses in peripheral blood, anti-PD-1 and anti-PD-L1 monoclonal antibodies are ideal as specific agents to augment T cell responses to tumors with fewer adverse events than with the inhibition of CTLA-4, because the interaction of CTLA-4 with its ligands occurs in the priming phase of T cell responses within lymph nodes. In recent phase I clinical trials, objective responses were observed in patients with melanoma, renal cell carcinoma, and non-small cell lung cancer who underwent immunotherapy with an anti-PD-1 monoclonal antibody. In addition, the antitumor activity of an anti-PD-L1 monoclonal antibody was observed in patients with melanoma, renal cell carcinoma, non-small cell lung cancer, and ovarian cancer. The next frontier of immunotherapy targeting the PD-1 axis is to define patient selection criteria and explore combination therapy with other therapeutic manipulations such as adoptive immunotherapies.
authors.affiliation: Center for Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor