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

Linh T Nguyen; Pamela S Ohashi

doi:10.1038/nri3790

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

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

Authors

Linh T Nguyen¹, Pamela S Ohashi¹

Affiliation

¹ Immune Therapy Program, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada.

PMID: 25534622
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
Lymphocyte Activation Gene 3 Protein
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
Costimulatory and Inhibitory T-Cell Receptors
Ligands
Programmed Cell Death 1 Receptor
Lymphocyte Activation Gene 3 Protein
Lag3 protein, human