Kevin Bielamowicz, M.D., Arkansas Research Institute
2016, second year
Poor outcomes for children with high grade glioma (HGG) warrant novel therapeutic strategies, and redirecting immune cells can achieve this aim while minimizing side effects to normal cells. Using mathematical modeling in a group of brain tumor samples, we discovered substantial variation between individual cells within the same tumor as well as between individual tumors from different patients. This warranted a strategy that can target the largest number of glioma cells possible. We created a multispecific T cell therapeutic product for the treatment of HGG that targets three specific cell surface markers on tumor cells simultaneously. Analysis of a larger set of patient glioma samples shows that targeting these three tumor cell specific surface markers will target nearly all tumor cells in this patient population. In the laboratory and in mouse models this product shows improved antitumor function compared to T cell products that target fewer markers. The results of this study will hopefully enable a first-in-children clinical trial as well as serve as a platform for designing products for other childhood cancers, such as leukemia.