ENGINEERING T CELLS TARGETING GPC2 FOR TREATING NEUROBLASTOMA

Abstract Background and Significance Neuroblastoma is a rare pediatric cancer that forms in immature nerve tissue of infants accounts for 10 to 15 percent cancer-related deaths children. The five-year survival high-risk neuroblastoma 50% with current treatment practices being combination surgery, chemotherapy, radiation. A more effective therapy therefore needed improve overall patient outcomes. Methods CT3 mouse antibody targets GPC2 was previously identified the lab has shown activity chimeric antigen receptor (CAR) T cell format against neuroblastoma. Humanization also done through CDR grafting human germline sequences prevent potential adverse immunogenic effects when treating patients. In present study, humanized (hCT3) were engineered into cells based on gamma/delta TCR scaffold (called AbTCR). activities hCT3 AbTCRs tested luciferase-based killing assays xenograft models. Results Humanized retains comparable binding affinity GPC2. CAR showed its ability regress tumor expression mice. Furthermore, mice treated AbTCR regression while became free three weeks after treatment. Conclusions Overall, are very active combating tumors efficacy at low dosage indicates targeted promising therapeutic other positive cancers