Science Spotlight: New insight into LAG3’s checkpoint function

Beigene Ltd. (NASDAQ:ONC; HKEX:6160) and collaborators at Shanghaitech University unraveled the mechanism of LAG3’s immune checkpoint function, which could have implications for designing antibodies that block LAG3 or predicting patient response.

The authors of the Cell paper found that upon ligand engagement, LAG3 gets polyubiquitinated by E3 ligases from the CBL family. But instead of leading to degradation, the protein’s conformation is changed in a way that enables downstream signaling and inhibition of T cell function. This ubiquitination event is critical for LAG3-mediated suppression of antitumor immunity, and the prevention of LAG3 ubiquitination by antibodies correlates with their potency as checkpoint inhibitors...