RT Journal Article
SR Electronic
T1 Activation-inducible CAR expression enables precise control over engineered CAR T cell function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.08.515608
DO 10.1101/2022.11.08.515608
A1 Fraessle, Simon P.
A1 Tschulik, Claudia
A1 Effenberger, Manuel
A1 Cletiu, Vlad
A1 Gerget, Maria
A1 Schober, Kilian
A1 Busch, Dirk H.
A1 Germeroth, Lothar
A1 Stemberger, Christian
A1 Poltorak, Mateusz P.
YR 2022
UL http://biorxiv.org/content/early/2022/11/08/2022.11.08.515608.abstract
AB CAR T cell therapy is a rapidly growing area of oncological treatments having a potential of becoming standard care for multiple indications. Coincidently, CRISPR/Cas gene-editing technology is entering next-generation CAR T cell product manufacturing with the promise of more precise and more controllable cell modification methodology. The intersection of these medical and molecular advancements creates an opportunity for completely new ways of designing engineered cells to help overcome current limitations of cell therapy. In this manuscript we present proof-of-concept data for a novel engineered feedback loop. We manufactured activation-inducible CAR T cells with the help of CRISPR-mediated targeted integration. This new type of engineered T cells expresses the CAR gene dependent on their activation status. This artifice opens new possibilities to regulate CAR T cell function both in vitro and in vivo. We believe that such a physiological control system can be a powerful addition to the currently available toolbox of next-generation CAR constructs.Competing Interest StatementS.P.F., C.T., M.E., V.C., M.G., D.H.B., C.S., L.G. and M.P.P. are currently employed by Juno Therapeutics GmbH, A Bristol-Myers Squibb Company and own stocks of Bristol-Myers Squibb. L.G., C.S., and M.P.P. are listed as inventors on previously filed related patent applications.