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Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells

Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research (DZL), 80337 Munich, Germany
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(6), 1283; https://doi.org/10.3390/ijms20061283
Received: 20 February 2019 / Revised: 7 March 2019 / Accepted: 8 March 2019 / Published: 14 March 2019
Effective adoptive T cell therapy (ACT) comprises the killing of cancer cells through the therapeutic use of transferred T cells. One of the main ACT approaches is chimeric antigen receptor (CAR) T cell therapy. CAR T cells mediate MHC-unrestricted tumor cell killing by enabling T cells to bind target cell surface antigens through a single-chain variable fragment (scFv) recognition domain. Upon engagement, CAR T cells form a non-classical immune synapse (IS), required for their effector function. These cells then mediate their anti-tumoral effects through the perforin and granzyme axis, the Fas and Fas ligand axis, as well as the release of cytokines to sensitize the tumor stroma. Their persistence in the host and functional outputs are tightly dependent on the receptor’s individual components—scFv, spacer domain, and costimulatory domains—and how said component functions converge to augment CAR T cell performance. In this review, we bring forth the successes and limitations of CAR T cell therapy. We delve further into the current understanding of how CAR T cells are designed to function, survive, and ultimately mediate their anti-tumoral effects. View Full-Text
Keywords: chimeric antigen receptor; adoptive T cell therapy; cancer immunotherapy chimeric antigen receptor; adoptive T cell therapy; cancer immunotherapy
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MDPI and ACS Style

Benmebarek, M.-R.; Karches, C.H.; Cadilha, B.L.; Lesch, S.; Endres, S.; Kobold, S. Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells. Int. J. Mol. Sci. 2019, 20, 1283.

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