Abstract
Immunotherapy using CD47 blockade has shown promise in treating adult and pediatric malignant primary central nervous system tumors. We recently demonstrated that irradiation significantly enhanced anti-CD47-dependent phagocytosis of high-grade glioma cells in vitro. Furthermore, mice engrafted with high-grade human glioma that received anti-CD47 combined with irradiation showed a significant increase in the survival rate and a significant decrease in tumor growth than those that received a single treatment. However, the use of irradiation may result in potential toxicity to normal CNS cells that are not susceptible to macrophage phagocytosis in anti-CD47 monotherapy. We have now extended these studies to test the effect of combining anti-CD47 and irradiation on macrophage-mediated phagocytosis of central nervous system cells. We analyzed phagocytosis of normal human neural stem cells exposed to different irradiation doses in combination with anti-CD47 treatment to assess for the potential toxicity that uniquely exists with this treatment combination.