July 20, 2021, NEW YORK – A Ludwig Stanford study shows that blocking the signal transmitted by a protein named CD47 in a mouse model of HER2+ breast cancer increases the efficacy of trastuzumab (Herceptin)—a standard treatment for this malignancy—even when the cancer is resistant to the antibody therapy. Led by Irv Weissman, director of Ludwig Stanford and of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, the study was published July 20 in the Proceedings of the National Academy of Sciences. Weissman and his colleagues have previously shown that CD47 acts as a “don’t eat me” signal to immune cells known as macrophages, and that blocking that signal can stimulate a macrophage assault on tumors. In this study they show that combining trastuzumab and an anti-CD47 antibody therapy significantly inhibited tumor growth in mouse models of HER2+ breast cancer, and improved survival compared to either treatment alone. Most of the research on trastuzumab has focused on its recruitment of immune cells called natural killer (NK) cells to attack HER2-expressing cancer cells, but this study illuminates how trastuzumab also recruits macrophages to do the job.
The Stanford Medicine release on this discovery can be found here.