Clinical blockade of PD1 and LAG3--potential mechanisms of action

Nat Rev Immunol. 2015 Jan;15(1):45-56. doi: 10.1038/nri3790.

Abstract

Dysfunctional T cells can render the immune system unable to eliminate infections and cancer. Therapeutic targeting of the surface receptors that inhibit T cell function has begun to show remarkable success in clinical trials. In this Review, we discuss the potential mechanisms of action of the clinical agents that target two of these receptors, programmed cell death protein 1 (PD1) and lymphocyte activation gene 3 protein (LAG3). We also suggest correlative studies that may define the predominant mechanisms of action and identify predictive biomarkers.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, CD* / metabolism
  • Costimulatory and Inhibitory T-Cell Receptors / antagonists & inhibitors
  • Humans
  • Ligands
  • Molecular Targeted Therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / metabolism
  • Protein Binding
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • CD223 antigen
  • Costimulatory and Inhibitory T-Cell Receptors
  • Ligands
  • Programmed Cell Death 1 Receptor