Journal Article

LAG-3 as the third checkpoint inhibitor

Vignali, Dario A. A., Aggarwal, Vaishali, Workman, Creg J.

2023

Overview

Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that is highly expressed by exhausted T cells. LAG-3 is a promising immunotherapeutic target, with more than 20 LAG-3-targeting therapeutics in clinical trials and a fixed-dose combination of anti-LAG-3 and anti-PD-1 now approved to treat unresectable or metastatic melanoma. Although LAG-3 is widely recognized as a potent inhibitory receptor, important questions regarding its biology and mechanism of action remain. In this Perspective, we focus on gaps in the understanding of LAG-3 biology and discuss the five biggest topics of current debate and focus regarding LAG-3, including its ligands, signaling and mechanism of action, its cell-specific functions, its importance in different disease settings, and the development of novel therapeutics. LAG-3 is a T cell inhibitory receptor with a lot of promise as a target for immunotherapy, but considerable research will be needed to fully understand the nuances of this receptor and how best to target it, as outlined in this Perspective.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/1619/554 / 631/250/251/1574 / 631/250/580/1884 / 692/699/67/580 / Antigens / Antigens, CD - genetics / Biology / Biomedical and Life Sciences / Biomedicine / CD223 antigen / Cell activation / Cell cycle / Clinical trials / Disease / Drug development / FDA approval / Humans / Immune checkpoint inhibitors / Immunology / Immunotherapy / Infectious Diseases / Kinases / Lectins / Ligands / Lymphocyte Activation Gene 3 Protein / Lymphocytes / Lymphocytes T / Melanoma / Melanoma - drug therapy / Metastases / Metastasis / PD-1 protein / Perspective / Physiology / Regulatory approval / T-Lymphocytes