Nature: LAG-3, the next outlet?

On March 18, 2022, the FDA officially approved the "first-in-class" product Opdualag of lymphocyte-activation gene-3 (LAG-3) for the treatment of patients with unresectable or metastatic melanoma.

LAG-3 structure (source: Immunological Reviews)

Professor Frédéric Triebel discovered LAG-3 in the late 1980s

Some listed and under-development LAG-3 projects (Source: Nature Reviews Drug Discovery)

*Relatlimab was approved for marketing on March 18, 2022

"This is a transformative data," said Jason Luke, an oncologist at the University of Pittsburgh Medical Center who has advised BMS after the Phase II/III data for relatlimab and nivolumab

From being left out, to counterattack

BMS began focusing on the immune checkpoint field as early as 2010 and attempted to initiate a clinical trial of Relatlimab in 2013

greater potential

Another therapeutic potential of LAG-3 is whether other tumors will respond positively to combined LAG-3 and PD-1 therapy

Tumors were classified based on immune scores

However, pharmacologist Adam Palmer from the University of North Carolina School of Medicine is skeptical

Competition is fierce

According to the NextPharma database, there are currently more than 20 LAG-3 products in clinical trials worldwide

future breakthrough

Up to now, more than 10 PD-1/PD-L1 monoclonal antibodies have been approved for marketing in the world, providing new treatment options for dozens of tumors

MHC II proteins, Galectin-3, LSECtin and FGL1 can all bind to LAG-3 (source: Seminars in Immunology)

These findings have brought new opportunities and challenges for drug development around LAG-3.

References:

[1] Asher Mullard.

[8] Liu Hao et al.
Research progress on the molecular biological function of lymphocyte activation gene 3 and its clinical application of antibody drugs.
Chinese Journal of Pharmacology and Toxicology.
2019.

[9] Jedd D.
Wolchok et al.
Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.
The New England Journal of Medicine.
2017.

[10] Jérôme Galon et al.
Approaches to treat immune hot, altered and cold tumors with combination immunotherapies.
Nature Reviews Drug Discovery.
2019.

[11] http:// [11] http:// [12] https://zhuanlan.
zhihu.
com/p/450850700

[13] Elisa Ruffo et al.
Lymphocyte-activationgene 3 (LAG3): The next immune check point receptor.
Seminars in Immunology.
2019.