by Researchers from Stanford University and New York University have made a significant breakthrough in understanding the structure and function of the LAG-3 protein, a key player in immune checkpoint regulation, which is crucial for developing new cancer treatments. The findings of their study, published in Proceedings of the National Academy of Sciences, shed light on important details of the LAG-3 molecule that could potentially enhance the effectiveness of immunotherapy targeting this protein.
LAG-3 is known to be exploited by certain cancerous tumors to evade immune recognition by creating a shield against the body’s natural defenses. By deciphering the intricate structure of LAG-3 at the atomic level, researchers can gain insights into how it interacts with other molecules and design therapies to disrupt its function effectively. This knowledge is critical for developing drugs that can effectively counteract the immune evasion strategies employed by cancer cells.
Unlike traditional chemical drugs, current immunotherapies harness lab-manufactured antibodies to target specific immune checkpoint proteins like LAG-3. By blocking these checkpoints, the therapies enable the immune system to recognize and attack cancer cells once again. While antibodies targeting other checkpoint proteins have been successfully developed and approved for use, LAG-3 presents a unique challenge due to its complex structure and function.
The research team, led by co-senior author Jennifer Cochran and Ph.D. student Jack Silberstein, embarked on a rigorous three-year journey to unravel the mysteries of LAG-3. Using X-ray crystallography, a delicate technique that requires growing crystals of the protein and bombarding them with X-ray beams, the team finally succeeded in obtaining a detailed 3D image of the LAG-3 molecule. This breakthrough revealed that LAG-3 exists as a dimer, with two molecules coming together to form the functional checkpoint protein.
Further experiments conducted by the collaborators at New York University, led by MD, Ph.D. student Jasper Du and Assistant Professor Jun Wang, provided crucial insights into how antibodies targeting LAG-3 disrupt its activity by binding to specific regions of the protein. These findings offer promising avenues for developing more effective therapies that can block LAG-3 and enhance the immune system’s ability to combat cancer.
As researchers continue to uncover the complexities of LAG-3 and its role in immune regulation, the prospect of developing innovative treatments that target this protein holds great promise in the fight against cancer. By combining insights from basic science discoveries with medical innovations, a multifaceted approach involving surgery, chemotherapy, and immunotherapy could pave the way for more personalized and effective cancer treatments in the future.
