Game Changer Grant Awarded to Sujatha Venkataraman

Diffuse Intrinsic Pontine Glioma (DIPG) is one of the most aggressive brain tumors in children. Regrettably, the 5-year survival rate has held steady at 0% since the 1950s, as various attempts to develop therapies to improve local control or survival have been unsuccessful. Recently, Chimeric Antigen Receptor (CAR) T cells targeting DIPG have shown promise in preclinical models and are in development for clinical trials. A major obstacle in the CAR-T cell therapy for solid tumors is the absence of true “tumor only” antigens as most antigens are shared among multiple normal cells. To overcome this risk, we have successfully generated and tested the functionality of a novel “logic gated” CAR-T cells targeting two distinct antigens, CD56 and CD99 that are highly expressed on DIPG cells. This novel gated CAR-T cells will have full activation against DIPG cells having both the antigens while sparing the single antigen expressing normal cells. We will now investigate the safety and the preclinical efficacy of the novel logic gated CAR-T cells against DIPG and evaluate its translational relevance to DIPG patients.