Stimulating Macrophages to Eat Pediatric Brain Cancer: Combining Anti-CD47 and Irradiation to Enhance the Treatment of Group 3 Medulloblastoma

University of Utah, Salt Lake City, UT

We devolved a therapy that allows macrophages (a type of white blood cell) to specifically “eat” tumor cells by a process called phagocytosis. The therapy, anti-CD47 treatment, blocks a signal on tumor cells called a “Don’t Eat Me” signal. There are also signals on tumor cells that promote phagocytosis of tumor cells called “Eat Me” signals. We know that increasing “Eat Me” signals (when the “Don’t Eat Me” signal is being suppressed by anti-CD47) greatly enhances the ability of macrophages to “eat” tumor cells. Irradiation is well known to enhance the expression of “Eat Me” signals on tumor cells, and we have preliminary data show that the combination of anti-CD47 and irradiation can enhance eating of malignant brain tumor by macrophages in the test tube, as well as in a live animal. Here, we propose to use this combination (anti-CD47 + irradiation) to kill the deadly pediatric brain tumor, Group 3 Medulloblastoma. We will determine the dose of irradiation needed to enhance anti-CD47 meditated eating of Group 3 Medulloblastoma cells by macrophages in test tubes and live animals. In addition, we will determine how irradiation with anti-CD47 can impact the levels of “Eat Me” and “Don’t Eat Me” signals on Group 3 medulloblastoma tumor cells. Our goal is to utilize this combination to dial down the amount of irradiation needed to treat the children with Group 3 medulloblastoma. This will allow for a more effective therapy that is also safer.