Precigen’s UltraCAR-T platform shows antitumor eefficacy in preclinical data

Precigen presented preclinical data for the next generation UltraCAR-T platform utilizing MSLN CAR from Precigen’s library of non-viral plasmids at the American Association for Cancer Research Annual Meeting. Next generation MSLN UltraCAR-T cells were successfully engineered using a single multicistronic non-viral transposon and overnight manufacturing process to simultaneously express a CAR, mbIL15, a kill switch, and a novel mechanism for intrinsic PD-1 blockade. Next generation MSLN UltraCAR-T cells showed specific and significant downregulation of PD-1 leading to significant increase in cytotoxicity of MSLN+ PD-L1+ tumor cells in vitro at low effector to target cell ratios compared to control MSLN CAR-T cells lacking PD-1 blockade. Next generation MSLN UltraCAR-T cells exhibited markedly enhanced polyfunctionality as well as enhanced inflammatory cytokine production in the presence of MSLN+ PD-L1+ tumor cells. In two different in vivo xenograft models, a single administration of next generation MSLN UltraCAR-T cells to tumor bearing mice resulted in robust UltraCAR-T cell expansion and durable persistence leading to significant antitumor efficacy. Rechallenging the previously treated mice who became tumor-free for a second time with mesothelioma tumors to simulate tumor relapse led to the significant reduction in tumor burden without additional MSLN UltraCAR-T treatment demonstrating the durable persistence and functionality of UltraCAR-T cells in vivo.