Tumor cells outsmart the immune system by using their proteins to stimulate certain receptors on immune cells—interactions, referred to as “checkpoints,” that put the brakes on immune attack. So-called checkpoint inhibitor drugs prevent those interactions by inactivating the tumor proteins or their immune-cell receptors. The checkpoint protein B7-H3 is overexpressed in the vast majority of human cancers, correlates with poor clinical outcomes, and is now being targeted in cancer-treatment trials.
In a study published online on April 27 in Science Advances, Xingxing Zang, M.Med., Ph.D., and colleagues report that B7-H3 is also highly expressed in both mouse and human adipose (fat) tissue, with the highest levels found in precursors that develop into fat cells. In mice in which the gene for B7-H3 was knocked out, obesity developed spontaneously along with inflammation of fat tissue and metabolic dysfunction. Dr. Zang had previously found that B7-H3 is an immune checkpoint and therefore a therapeutic target in human cancers. His Science Advances paper reveals an unexpected metabolic role for B7-H3 in fat tissue, opening up the possibility of treating obesity and other metabolic diseases by modifying the B7-H3 pathway.
Dr. Zang is professor of microbiology & immunology, of medicine, and of urology, the Louis Goldstein Swan Chair in Cancer Research at Einstein. He is a member of the National Cancer Institute-designated Montefiore Einstein Cancer Center and is also a member of the Einstein-Mount Sinai Diabetes Research Center. The study’s first author is Elodie Picarda, Ph.D., associate in the department of microbiology & immunology and in the laboratory of Dr. Zang at Einstein.
Albert Einstein College of Medicine has filed two patent applications related to B7-H3 antibody and CAR-T therapy and is seeking licensing partners to further develop and commercialize these technologies. Interested parties can contact the Office of Biotechnology and Business Development at biotech@einsteinmed.edu
Posted on: Wednesday, April 27, 2022
