Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
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
_version_ 1784830640005316608
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
work_keys_str_mv AT werchauniels combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT kotterbettina combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT criadomoronatielvira combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT gosselinkandre combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT cordesnicole combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT lockdominik combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT lennartzsimon combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT kolbecarolin combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT winternora combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT teppertkarin combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT engertfabian combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT websterbrian combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT mittelstaetjoerg combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT schaeferdaniel combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT mallmannpeter combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT mallmannmichaelr combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT ratiudominik combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT assenmachermario combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT schaserthomas combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT vonbergweltbaildonmichael combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT abramowskipierre combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells
AT kaiserandrewd combinedtargetingofsolublelatenttgfßandasolidtumorassociatedantigenwithadaptercartcells