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Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells
Solid tumors consist of malignant and nonmalignant cells that together create the local tumor microenvironment (TME). Additionally, the TME is characterized by the expression of numerous soluble factors such as TGF-β. TGF-β plays an important role in the TME by suppressing T cell effector function a...
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/PMC9662194/ https://www.ncbi.nlm.nih.gov/pubmed/36387056 http://dx.doi.org/10.1080/2162402X.2022.2140534 |
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author | Werchau, Niels Kotter, Bettina Criado-Moronati, Elvira Gosselink, Andre Cordes, Nicole Lock, Dominik Lennartz, Simon Kolbe, Carolin Winter, Nora Teppert, Karin Engert, Fabian Webster, Brian Mittelstaet, Joerg Schaefer, Daniel Mallmann, Peter Mallmann, Michael R. Ratiu, Dominik Assenmacher, Mario Schaser, Thomas von Bergwelt-Baildon, Michael Abramowski, Pierre Kaiser, Andrew D. |
author_facet | Werchau, Niels Kotter, Bettina Criado-Moronati, Elvira Gosselink, Andre Cordes, Nicole Lock, Dominik Lennartz, Simon Kolbe, Carolin Winter, Nora Teppert, Karin Engert, Fabian Webster, Brian Mittelstaet, Joerg Schaefer, Daniel Mallmann, Peter Mallmann, Michael R. Ratiu, Dominik Assenmacher, Mario Schaser, Thomas von Bergwelt-Baildon, Michael Abramowski, Pierre Kaiser, Andrew D. |
author_sort | Werchau, Niels |
collection | PubMed |
description | Solid tumors consist of malignant and nonmalignant cells that together create the local tumor microenvironment (TME). Additionally, the TME is characterized by the expression of numerous soluble factors such as TGF-β. TGF-β plays an important role in the TME by suppressing T cell effector function and promoting tumor invasiveness. Up to now CAR T cells exclusively target tumor-associated antigens (TAA) located on the cell membrane. Thus, strategies to exploit soluble antigens as CAR targets within the TME are needed. This study demonstrates a novel approach using Adapter CAR (AdCAR) T cells for the detection of soluble latent TGF-β within the TME of a pancreatic tumor model. We show that AdCARs in combination with the respective adapter can be used to sense soluble tumor-derived latent TGF-β, both in vitro and in vivo. Sensing of the soluble antigen induced cellular activation and effector cytokine production in AdCAR T cells. Moreover, we evaluated AdCAR T cells for the combined targeting of soluble latent TGF-β and tumor cell killing by targeting CD66c as TAA in vivo. In sum, our study broadens the spectrum of targetable moieties for AdCAR T cells by soluble latent TGF-β. |
format | Online Article Text |
id | pubmed-9662194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-96621942022-11-15 Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells Werchau, Niels Kotter, Bettina Criado-Moronati, Elvira Gosselink, Andre Cordes, Nicole Lock, Dominik Lennartz, Simon Kolbe, Carolin Winter, Nora Teppert, Karin Engert, Fabian Webster, Brian Mittelstaet, Joerg Schaefer, Daniel Mallmann, Peter Mallmann, Michael R. Ratiu, Dominik Assenmacher, Mario Schaser, Thomas von Bergwelt-Baildon, Michael Abramowski, Pierre Kaiser, Andrew D. Oncoimmunology Original Research Solid tumors consist of malignant and nonmalignant cells that together create the local tumor microenvironment (TME). Additionally, the TME is characterized by the expression of numerous soluble factors such as TGF-β. TGF-β plays an important role in the TME by suppressing T cell effector function and promoting tumor invasiveness. Up to now CAR T cells exclusively target tumor-associated antigens (TAA) located on the cell membrane. Thus, strategies to exploit soluble antigens as CAR targets within the TME are needed. This study demonstrates a novel approach using Adapter CAR (AdCAR) T cells for the detection of soluble latent TGF-β within the TME of a pancreatic tumor model. We show that AdCARs in combination with the respective adapter can be used to sense soluble tumor-derived latent TGF-β, both in vitro and in vivo. Sensing of the soluble antigen induced cellular activation and effector cytokine production in AdCAR T cells. Moreover, we evaluated AdCAR T cells for the combined targeting of soluble latent TGF-β and tumor cell killing by targeting CD66c as TAA in vivo. In sum, our study broadens the spectrum of targetable moieties for AdCAR T cells by soluble latent TGF-β. Taylor & Francis 2022-11-11 /pmc/articles/PMC9662194/ /pubmed/36387056 http://dx.doi.org/10.1080/2162402X.2022.2140534 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 Werchau, Niels Kotter, Bettina Criado-Moronati, Elvira Gosselink, Andre Cordes, Nicole Lock, Dominik Lennartz, Simon Kolbe, Carolin Winter, Nora Teppert, Karin Engert, Fabian Webster, Brian Mittelstaet, Joerg Schaefer, Daniel Mallmann, Peter Mallmann, Michael R. Ratiu, Dominik Assenmacher, Mario Schaser, Thomas von Bergwelt-Baildon, Michael Abramowski, Pierre Kaiser, Andrew D. Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells |
title | Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells |
title_full | Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells |
title_fullStr | Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells |
title_full_unstemmed | Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells |
title_short | Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells |
title_sort | combined targeting of soluble latent tgf-ß and a solid tumor-associated antigen with adapter car t cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662194/ https://www.ncbi.nlm.nih.gov/pubmed/36387056 http://dx.doi.org/10.1080/2162402X.2022.2140534 |
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