Endowing Universal CAR T-cell with Immune-Evasive Properties using TALEN-Gene Editing.
S. Jo, S. Das, A. Williams, A.-s. Chretien, T. Pagliardini, A. Leroy, j. postigo-fernandez, D. leclerre, B. jahangiri, i. chion-sotinel, A. Gouble, M. Dusseaux, r. Galetto, a. Duclert, E. Marcenaro, R. Devillier, D. Olive, p. Duchateau, L. Poirot, J. Valton
Abstract
Universal CAR T-cell therapies are poised to revolutionize cancer treatment and to improve patient outcomes. However, realizing these advantages in an allogeneic setting requires universal CAR T-cells that can kill target tumor cells, avoid depletion by the host immune system, and proliferate without attacking host tissues. Here, we describe the development of a novel immune-evasive CAR T-cells scaffold that evades NK cell and alloresponsive T-cell attacks and imparts efficient antitumor activity in vitro and in vivo. This scaffold could enable the broad use of universal CAR T-cells in allogeneic settings and holds great promise for future powerful clinical applications.
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