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Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells

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 targ...

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Autores principales: Benmebarek, Mohamed-Reda, Karches, Clara Helke, Cadilha, Bruno Loureiro, Lesch, Stefanie, Endres, Stefan, Kobold, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470706/
https://www.ncbi.nlm.nih.gov/pubmed/30875739
http://dx.doi.org/10.3390/ijms20061283
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author Benmebarek, Mohamed-Reda
Karches, Clara Helke
Cadilha, Bruno Loureiro
Lesch, Stefanie
Endres, Stefan
Kobold, Sebastian
author_facet Benmebarek, Mohamed-Reda
Karches, Clara Helke
Cadilha, Bruno Loureiro
Lesch, Stefanie
Endres, Stefan
Kobold, Sebastian
author_sort Benmebarek, Mohamed-Reda
collection PubMed
description 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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spelling pubmed-64707062019-04-26 Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells Benmebarek, Mohamed-Reda Karches, Clara Helke Cadilha, Bruno Loureiro Lesch, Stefanie Endres, Stefan Kobold, Sebastian Int J Mol Sci Review 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. MDPI 2019-03-14 /pmc/articles/PMC6470706/ /pubmed/30875739 http://dx.doi.org/10.3390/ijms20061283 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Benmebarek, Mohamed-Reda
Karches, Clara Helke
Cadilha, Bruno Loureiro
Lesch, Stefanie
Endres, Stefan
Kobold, Sebastian
Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells
title Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells
title_full Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells
title_fullStr Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells
title_full_unstemmed Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells
title_short Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells
title_sort killing mechanisms of chimeric antigen receptor (car) t cells
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470706/
https://www.ncbi.nlm.nih.gov/pubmed/30875739
http://dx.doi.org/10.3390/ijms20061283
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