PT  - JOURNAL ARTICLE
AU  - Fraessle, Simon P.
AU  - Tschulik, Claudia
AU  - Effenberger, Manuel
AU  - Cletiu, Vlad
AU  - Gerget, Maria
AU  - Schober, Kilian
AU  - Busch, Dirk H.
AU  - Germeroth, Lothar
AU  - Stemberger, Christian
AU  - Poltorak, Mateusz P.
TI  - Activation-inducible CAR expression enables precise control over engineered CAR T cell function
AID  - 10.1101/2022.11.08.515608
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.08.515608
4099  - http://biorxiv.org/content/early/2022/11/08/2022.11.08.515608.short
4100  - http://biorxiv.org/content/early/2022/11/08/2022.11.08.515608.full
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.