New immunotherapies targeting the PD-1 pathway

Trends Pharmacol Sci. 2015 Sep;36(9):587-95. doi: 10.1016/j.tips.2015.06.005. Epub 2015 Jul 7.

Abstract

Ligands from the B7 family bind to receptors of the CD28 family, which regulate early T cell activation in lymphoid organs and control inflammation and autoimmunity in peripheral tissues. Programmed death-1 (PD-1), a member of the CD28 family, is an inhibitory receptor on T cells and is responsible for their dysfunction in infectious diseases and cancers. The complex mechanisms controlling the expression and signaling of PD-1 and programmed death ligand 1 (PD-L1) are emerging. Recently completed and ongoing clinical trials that target these molecules have shown remarkable success by generating durable clinical responses in some cancer patients. In chronic viral infections, preclinical data reveal that targeting PD-1 and its ligands can improve T cell responses and virus clearance. There is also promise in stimulating this pathway for the treatment of autoimmune and inflammatory disorders.

Keywords: PD-1; PD-L1; PD-L2; cancer; immunotherapy; viral infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / immunology*
  • Antineoplastic Agents / therapeutic use
  • Antiviral Agents / immunology*
  • Antiviral Agents / therapeutic use
  • Humans
  • Immunotherapy / methods*
  • Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology*
  • Virus Diseases / therapy*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Antiviral Agents
  • Programmed Cell Death 1 Receptor