title: Programmed death-1 inhibition in renal cell carcinoma: clinical insights and future directions.
abstract: The treatment of metastatic renal cell carcinoma (mRCC) has evolved markedly over the past decade, broaden- ing beyond immune-based strategies (eg, interleukin-2 and interferon-α) to include targeted agents (eg, sunitinib [Sutent, Pfizer] and sorafenib [Nexavar, Bayer]). Recently, there has been a renewed interest in immune-based strategies, with clinical trials underway to assess vaccines and other immunomodulatory agents. Of particular interest are agents that inhibit the interaction between the programmed death-1 (PD-1) receptor and its ligand (PD-L1) at the T-cell/antigen-presenting cell interface. This interaction produces T-cell anergy and therefore stifles the antitumor immune response. Monoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development. The clinical trajectory of these agents is discussed herein, with specific attention to the potential placement of PD-1/ PD-L1 inhibition in the crowded therapeutic landscape of mRCC.
authors.affiliation: City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.affiliation: City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: Adriana
authors.initials: A
authors.lastname: Hu
authors.affiliation: City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Chang
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D061026:Programmed Cell Death 1 Receptor