EXTH-23. BICISTRONIC CAR-T CELLS TARGETING EGFR AND IL13RΑ2 MITIGATE ANTIGENIC HETEROGENEITY IN GLIOMA

Abstract Chimeric antigen receptor (CAR)-T cells have had a significant effect in hematological diseases, with recent study confirming that the can last for ten years vivo. Unfortunately, to date, CAR-T little solid tumors. One cause of treatment difficulty is antigenic heterogeneity. Our experience glioblastoma suggests addressing heterogeneity may improve clinical efficacy. Targeting epidermal growth factor (EGFR) and interleukin 13 subunit alpha 2 (IL13Rα2) individually could lead tumor control short term, but it will be marked by recurrence through loss or downregulation long term. This resistance mechanism inhibited combinatorial targeting. To this end, we designed bicistronic construct targets both EGFR IL13Rα2 simultaneously, decrease potential escape recurrence. The employ an “OR” logic gate modify T kill vitro vivo, order retain effectiveness when one target lost second still present. experimental results demonstrate validate safety possibility translation. In addition, efficiency transfecting single vector was higher than two vectors on monovalent CARs. summary, structure promising strategy address problem targeting tumors potentially level barriers targeted T-cell therapy. Educational Objectives: After completion, participants able explain importance context escape. Participants also identify reducing implementation