Rapidly Switchable Universal CAR-T Cells for Treatment of CD123-Positive Leukemia
Simon Loff, Josephine Dietrich, Jan-Erik Meyer, Julia Riewaldt, Johannes Spehr, Malte von Bonin, Cordula Gründer, Mridula Swayampakula, Kristin Franke, Anja Feldmann, Michael Bachmann, Gerhard Ehninger, Armin Ehninger, Marc Cartellieri
Abstract
. We further demonstrated a pre-clinical proof of concept for the safety-switch mechanism using a hematotoxicity mouse model wherein TM123-redirected UniCAR-T showed reversible toxicity toward hematopoietic cells compared to CD123 CAR-T. In conclusion, UniCAR-T maintain full anti-leukemic efficacy, while ensuring rapid controllability to improve safety and versatility of CD123-directed immunotherapy. The safety and efficacy of UniCAR-T in combination with TM123 will now be assessed in a phase I clinical trial (ClinicalTrials.gov: NCT04230265).