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Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure
Chimeric antigen receptor (CAR) T cell therapies have resulted in profound clinical responses in the treatment of CD19-positive hematological malignancies, but a significant proportion of patients do not respond or relapse eventually. As an alternative to CAR T cells, T cells can be engineered to ex...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812760/ https://www.ncbi.nlm.nih.gov/pubmed/35127255 http://dx.doi.org/10.1080/2162402X.2022.2033528 |
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author | Wachsmann, Tassilo L. A. Wouters, Anne K. Remst, Dennis F. G. Hagedoorn, Renate S. Meeuwsen, Miranda H. van Diest, Eline Leusen, Jeanette Kuball, Jürgen Falkenburg, J. H. Frederik Heemskerk, Mirjam H. M. |
author_facet | Wachsmann, Tassilo L. A. Wouters, Anne K. Remst, Dennis F. G. Hagedoorn, Renate S. Meeuwsen, Miranda H. van Diest, Eline Leusen, Jeanette Kuball, Jürgen Falkenburg, J. H. Frederik Heemskerk, Mirjam H. M. |
author_sort | Wachsmann, Tassilo L. A. |
collection | PubMed |
description | Chimeric antigen receptor (CAR) T cell therapies have resulted in profound clinical responses in the treatment of CD19-positive hematological malignancies, but a significant proportion of patients do not respond or relapse eventually. As an alternative to CAR T cells, T cells can be engineered to express a tumor-targeting T cell receptor (TCR). Due to HLA restriction of TCRs, CARs have emerged as a preferred treatment moiety when targeting surface antigens, despite the fact that functional differences between engineered TCR (eTCR) T and CAR T cells remain ill-defined. Here, we compared the activity of CAR T cells versus engineered TCR T cells in targeting the B cell malignancy-associated antigen CD20 as a function of antigen exposure. We found CAR T cells to be more potent effector cells, producing higher levels of cytokines and killing more efficiently than eTCR T cells in a short time frame. However, we revealed that the increase of antigen exposure significantly impaired CAR T cell expansion, a phenotype defined by high expression of coinhibitory molecules and effector differentiation. In contrast, eTCR T cells expanded better than CAR T cells under high antigenic pressure, with lower expression of coinhibitory molecules and maintenance of an early differentiation phenotype, and comparable clearance of tumor cells. |
format | Online Article Text |
id | pubmed-8812760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-88127602022-02-04 Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure Wachsmann, Tassilo L. A. Wouters, Anne K. Remst, Dennis F. G. Hagedoorn, Renate S. Meeuwsen, Miranda H. van Diest, Eline Leusen, Jeanette Kuball, Jürgen Falkenburg, J. H. Frederik Heemskerk, Mirjam H. M. Oncoimmunology Original Research Chimeric antigen receptor (CAR) T cell therapies have resulted in profound clinical responses in the treatment of CD19-positive hematological malignancies, but a significant proportion of patients do not respond or relapse eventually. As an alternative to CAR T cells, T cells can be engineered to express a tumor-targeting T cell receptor (TCR). Due to HLA restriction of TCRs, CARs have emerged as a preferred treatment moiety when targeting surface antigens, despite the fact that functional differences between engineered TCR (eTCR) T and CAR T cells remain ill-defined. Here, we compared the activity of CAR T cells versus engineered TCR T cells in targeting the B cell malignancy-associated antigen CD20 as a function of antigen exposure. We found CAR T cells to be more potent effector cells, producing higher levels of cytokines and killing more efficiently than eTCR T cells in a short time frame. However, we revealed that the increase of antigen exposure significantly impaired CAR T cell expansion, a phenotype defined by high expression of coinhibitory molecules and effector differentiation. In contrast, eTCR T cells expanded better than CAR T cells under high antigenic pressure, with lower expression of coinhibitory molecules and maintenance of an early differentiation phenotype, and comparable clearance of tumor cells. Taylor & Francis 2022-02-01 /pmc/articles/PMC8812760/ /pubmed/35127255 http://dx.doi.org/10.1080/2162402X.2022.2033528 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Wachsmann, Tassilo L. A. Wouters, Anne K. Remst, Dennis F. G. Hagedoorn, Renate S. Meeuwsen, Miranda H. van Diest, Eline Leusen, Jeanette Kuball, Jürgen Falkenburg, J. H. Frederik Heemskerk, Mirjam H. M. Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure |
title | Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure |
title_full | Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure |
title_fullStr | Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure |
title_full_unstemmed | Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure |
title_short | Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure |
title_sort | comparing car and tcr engineered t cell performance as a function of tumor cell exposure |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812760/ https://www.ncbi.nlm.nih.gov/pubmed/35127255 http://dx.doi.org/10.1080/2162402X.2022.2033528 |
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