Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells
by
Mohamed-Reda Benmebarek †, Clara Helke Karches †, Bruno Loureiro Cadilha
, Stefanie Lesch, Stefan Endres and Sebastian Kobold *
Mohamed-Reda Benmebarek †, Clara Helke Karches †, Bruno Loureiro Cadilha, Stefanie Lesch, Stefan Endres and Sebastian Kobold *
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
*
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
(This article belongs to the Special Issue Apoptosis and Autophagy: The Double Edge in Cancer Development and Progression and in Other Human Diseases)
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.
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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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