This research calls into the question the design of LAG-blocking therapeutics in development," said Vignali, who is also associate director for scientific strategy and co-leader of the Cancer Immunology & Immunotherapy Program at UPMC Hillman Cancer Center. "They obviously work, but do they work optimally? They've been designed to block Class II interactions, but this study shows that LAG3 can function in absence of Class II."
"Now that we know LAG3 binds to the T cell receptor, we might be able to generate optimal blockers that target this interaction," he added.
Beyond cancer, Vignali said that the research could inform new treatment approaches for autoimmune and inflammatory disorders. Because these diseases are caused by overactive immune response, potential drugs could enhance—rather than block—LAG3 activity.
"To help the body fight cancer, you want to release the immune system brakes," explained Vignali. "But for autoimmunity, you want to pump the brakes harder."
