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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2140534 |
| _version_ | 1818470779913764864 |
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| author | Niels Werchau Bettina Kotter Elvira Criado-Moronati Andre Gosselink Nicole Cordes Dominik Lock Simon Lennartz Carolin Kolbe Nora Winter Karin Teppert Fabian Engert Brian Webster Joerg Mittelstaet Daniel Schaefer Peter Mallmann Michael R. Mallmann Dominik Ratiu Mario Assenmacher Thomas Schaser Michael von Bergwelt-Baildon Pierre Abramowski Andrew D. Kaiser |
| author_facet | Niels Werchau Bettina Kotter Elvira Criado-Moronati Andre Gosselink Nicole Cordes Dominik Lock Simon Lennartz Carolin Kolbe Nora Winter Karin Teppert Fabian Engert Brian Webster Joerg Mittelstaet Daniel Schaefer Peter Mallmann Michael R. Mallmann Dominik Ratiu Mario Assenmacher Thomas Schaser Michael von Bergwelt-Baildon Pierre Abramowski Andrew D. Kaiser |
| author_sort | Niels Werchau |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T21:41:57Z |
| format | Article |
| id | doaj.art-c33c72814d7043f49b55860008ccb5cf |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-04-13T21:41:57Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-c33c72814d7043f49b55860008ccb5cf2022-12-22T02:28:44ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2022.2140534Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cellsNiels Werchau0Bettina Kotter1Elvira Criado-Moronati2Andre Gosselink3Nicole Cordes4Dominik Lock5Simon Lennartz6Carolin Kolbe7Nora Winter8Karin Teppert9Fabian Engert10Brian Webster11Joerg Mittelstaet12Daniel Schaefer13Peter Mallmann14Michael R. Mallmann15Dominik Ratiu16Mario Assenmacher17Thomas Schaser18Michael von Bergwelt-Baildon19Pierre Abramowski20Andrew D. Kaiser21Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyDepartment of Obstetrics and Gynecology, University Hospital Cologne and Medical Faculty, Cologne, GermanyDepartment of Obstetrics and Gynecology, University Hospital Cologne and Medical Faculty, Cologne, GermanyDepartment of Obstetrics and Gynecology, University Hospital Cologne and Medical Faculty, Cologne, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyDepartment of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanySolid 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.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2140534ImmunotherapyCAR T cellsadapter CARTGF-β |
| spellingShingle | Niels Werchau Bettina Kotter Elvira Criado-Moronati Andre Gosselink Nicole Cordes Dominik Lock Simon Lennartz Carolin Kolbe Nora Winter Karin Teppert Fabian Engert Brian Webster Joerg Mittelstaet Daniel Schaefer Peter Mallmann Michael R. Mallmann Dominik Ratiu Mario Assenmacher Thomas Schaser Michael von Bergwelt-Baildon Pierre Abramowski Andrew D. Kaiser Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells OncoImmunology Immunotherapy CAR T cells adapter CAR TGF-β |
| 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 | Immunotherapy CAR T cells adapter CAR TGF-β |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2140534 |
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