Email Address:sujatha.venkataraman@cuanschutz.edu

Development of Gated Dual-antigen Targeting CAR-T Cell Therapy to Treat ATRT, an Aggressive Brain Tumor in Children

This project aims to address the high unmet needs in atypical teratoid/rhabdoid tumor (ATRT) which is a highly aggressive childhood brain tumor with a 5-year survival rate of 35%. Current treatments, including intensive chemotherapy, radiation, and stem cell transplants, result in significant toxicity and poor outcomes. The loss of the SMARCB1 gene, leading to epigenetic dysregulation, is a key feature of ATRT. Targeting SMARCB1 loss has been challenging, necessitating new therapies. ATRT cells uniquely express high levels of B7-H3 and EphA2 antigens. To avoid off-target toxicities, the team proposes developing CAR T cells that recognize both antigens using a bicistronic CAR construct with Boolean logic “AND” rules, ensuring specificity to ATRT cells while protecting normal tissues. Collaborators: Sujatha Venkataraman, PhD and Rajeev Vibhakar, MD, PhD, MPH/MSPH