Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells.

Autor:	Werchau N; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.; Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany., Kotter B; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Criado-Moronati E; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Gosselink A; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Cordes N; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Lock D; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Lennartz S; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Kolbe C; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Winter N; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Teppert K; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Engert F; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Webster B; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Mittelstaet J; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Schaefer D; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Mallmann P; Department of Obstetrics and Gynecology, University Hospital Cologne and Medical Faculty, Cologne, Germany., Mallmann MR; Department of Obstetrics and Gynecology, University Hospital Cologne and Medical Faculty, Cologne, Germany., Ratiu D; Department of Obstetrics and Gynecology, University Hospital Cologne and Medical Faculty, Cologne, Germany., Assenmacher M; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Schaser T; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., von Bergwelt-Baildon M; Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany., Abramowski P; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany., Kaiser AD; Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2022 Nov 11; Vol. 11 (1), pp. 2140534. Date of Electronic Publication: 2022 Nov 11 (Print Publication: 2022).
DOI:	10.1080/2162402X.2022.2140534
Abstrakt:	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. Competing Interests: 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, Mario Assenmacher, Thomas Schaser, Pierre Abramowski, Andrew D. Kaiser were employees of Miltenyi Biotec B.V. & Co. KG at the time the study was conducted. Niels Werchau, Bettina Kotter, Joerg Mittelstaet, and Andrew D. Kaiser are coinventors of a patent application focusing on sensing of soluble antigens with adapter CAR technology. Joerg Mittelstaet and Andrew D. Kaiser are coinventors of a patent application focusing on adapter CAR technology. Michael von Bergwelt-Baildon: Astellas Pharma, Bristol-Myers Squibb, Kite Gilead, Miltenyi Biotec, MOLOGEN, MSD, Novartis, Roche (Honoraria, Speakers’ Bureau, Research Funding, Travel, Accomodations, Expenses). (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu