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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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”. |
format | Online Article Text |
id | pubmed-9739809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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