A study led by Ludwig Stanford’s Irv Weissman published in July in the Proceedings of the National Academy of Sciences preclinically validated a potential combination therapy for breast cancer. Irv and his colleagues showed that targeting 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. Irv and his colleagues have previously shown that CD47 transmits a “don’t eat me” signal to the immune system’s macrophages, that several cancers express the protein for immune escape and that blocking that signal can stimulate a potent macrophage assault on tumors in mouse models of various cancers. They also helped develop an anti-CD47 antibody therapy (magrolimab) that is now in clinical development. Trastuzumab, meanwhile, works in part by recruiting another type of immune cell, the natural killer cell, to attack breast cancer cells. Irv and his team showed in this study that combining trastuzumab and magrolimab also engages macrophages in the antitumor attack. The dual therapy significantly inhibited tumor growth in mouse models of HER2+ breast cancer—including those resistant to trastuzumab—and improved survival compared to either treatment alone.
This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).