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Joining Forces for Cancer Treatment: From “TCR versus CAR” to “TCR and CAR”

T cell-based immunotherapy has demonstrated great therapeutic potential in recent decades, on the one hand, by using tumor-infiltrating lymphocytes (TILs) and, on the other hand, by engineering T cells to obtain anti-tumor specificities through the introduction of either engineered T cell receptors...

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Autores principales: Teppert, Karin, Wang, Xueting, Anders, Kathleen, Evaristo, César, Lock, Dominik, Künkele, Annette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739809/
https://www.ncbi.nlm.nih.gov/pubmed/36498890
http://dx.doi.org/10.3390/ijms232314563
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author Teppert, Karin
Wang, Xueting
Anders, Kathleen
Evaristo, César
Lock, Dominik
Künkele, Annette
author_facet Teppert, Karin
Wang, Xueting
Anders, Kathleen
Evaristo, César
Lock, Dominik
Künkele, Annette
author_sort Teppert, Karin
collection PubMed
description T cell-based immunotherapy has demonstrated great therapeutic potential in recent decades, on the one hand, by using tumor-infiltrating lymphocytes (TILs) and, on the other hand, by engineering T cells to obtain anti-tumor specificities through the introduction of either engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs). Given the distinct design of both receptors and the type of antigen that is encountered, the requirements for proper antigen engagement and downstream signal transduction by TCRs and CARs differ. Synapse formation and signal transduction of CAR T cells, despite further refinement of CAR T cell designs, still do not fully recapitulate that of TCR T cells and might limit CAR T cell persistence and functionality. Thus, deep knowledge about the molecular differences in CAR and TCR T cell signaling would greatly advance the further optimization of CAR designs and elucidate under which circumstances a combination of both receptors would improve the functionality of T cells for cancer treatment. Herein, we provide a comprehensive review about similarities and differences by directly comparing the architecture, synapse formation and signaling of TCRs and CARs, highlighting the knowns and unknowns. In the second part of the review, we discuss the current status of combining CAR and TCR technologies, encouraging a change in perspective from “TCR versus CAR” to “TCR and CAR”.
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spelling pubmed-97398092022-12-11 Joining Forces for Cancer Treatment: From “TCR versus CAR” to “TCR and CAR” Teppert, Karin Wang, Xueting Anders, Kathleen Evaristo, César Lock, Dominik Künkele, Annette Int J Mol Sci Review T cell-based immunotherapy has demonstrated great therapeutic potential in recent decades, on the one hand, by using tumor-infiltrating lymphocytes (TILs) and, on the other hand, by engineering T cells to obtain anti-tumor specificities through the introduction of either engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs). Given the distinct design of both receptors and the type of antigen that is encountered, the requirements for proper antigen engagement and downstream signal transduction by TCRs and CARs differ. Synapse formation and signal transduction of CAR T cells, despite further refinement of CAR T cell designs, still do not fully recapitulate that of TCR T cells and might limit CAR T cell persistence and functionality. Thus, deep knowledge about the molecular differences in CAR and TCR T cell signaling would greatly advance the further optimization of CAR designs and elucidate under which circumstances a combination of both receptors would improve the functionality of T cells for cancer treatment. Herein, we provide a comprehensive review about similarities and differences by directly comparing the architecture, synapse formation and signaling of TCRs and CARs, highlighting the knowns and unknowns. In the second part of the review, we discuss the current status of combining CAR and TCR technologies, encouraging a change in perspective from “TCR versus CAR” to “TCR and CAR”. MDPI 2022-11-23 /pmc/articles/PMC9739809/ /pubmed/36498890 http://dx.doi.org/10.3390/ijms232314563 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Teppert, Karin
Wang, Xueting
Anders, Kathleen
Evaristo, César
Lock, Dominik
Künkele, Annette
Joining Forces for Cancer Treatment: From “TCR versus CAR” to “TCR and CAR”
title Joining Forces for Cancer Treatment: From “TCR versus CAR” to “TCR and CAR”
title_full Joining Forces for Cancer Treatment: From “TCR versus CAR” to “TCR and CAR”
title_fullStr Joining Forces for Cancer Treatment: From “TCR versus CAR” to “TCR and CAR”
title_full_unstemmed Joining Forces for Cancer Treatment: From “TCR versus CAR” to “TCR and CAR”
title_short Joining Forces for Cancer Treatment: From “TCR versus CAR” to “TCR and CAR”
title_sort joining forces for cancer treatment: from “tcr versus car” to “tcr and car”
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739809/
https://www.ncbi.nlm.nih.gov/pubmed/36498890
http://dx.doi.org/10.3390/ijms232314563
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