Werchau, Niels ORCID: 0000-0001-7601-9179, Kotter, Bettina, Criado-Moronati, Elvira ORCID: 0000-0001-9124-7380, Gosselink, Andre ORCID: 0000-0003-0181-456X, Cordes, Nicole, Lock, Dominik ORCID: 0000-0002-3056-4582, Lennartz, Simon ORCID: 0000-0001-7202-398X, Kolbe, Carolin, Winter, Nora, Teppert, Karin ORCID: 0000-0002-2645-6781, 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 ORCID: 0000-0002-7121-6912 and Kaiser, Andrew D. (2022). Combined targeting of soluble latent TGF-beta and a solid tumor-associated antigen with adapter CAR T cells. OncoImmunology, 11 (1). PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 2162-402X

Full text not available from this repository.

Abstract

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-beta. TGF-beta 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-beta 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-beta, 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-beta 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-beta.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Werchau, NielsUNSPECIFIEDorcid.org/0000-0001-7601-9179UNSPECIFIED
Kotter, BettinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Criado-Moronati, ElviraUNSPECIFIEDorcid.org/0000-0001-9124-7380UNSPECIFIED
Gosselink, AndreUNSPECIFIEDorcid.org/0000-0003-0181-456XUNSPECIFIED
Cordes, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lock, DominikUNSPECIFIEDorcid.org/0000-0002-3056-4582UNSPECIFIED
Lennartz, SimonUNSPECIFIEDorcid.org/0000-0001-7202-398XUNSPECIFIED
Kolbe, CarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winter, NoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teppert, KarinUNSPECIFIEDorcid.org/0000-0002-2645-6781UNSPECIFIED
Engert, FabianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Webster, BrianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mittelstaet, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mallmann, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mallmann, Michael R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ratiu, DominikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assenmacher, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaser, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Von Bergwelt-Baildon, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abramowski, PierreUNSPECIFIEDorcid.org/0000-0002-7121-6912UNSPECIFIED
Kaiser, Andrew D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-674654
DOI: 10.1080/2162402X.2022.2140534
Journal or Publication Title: OncoImmunology
Volume: 11
Number: 1
Date: 2022
Publisher: TAYLOR & FRANCIS INC
Place of Publication: PHILADELPHIA
ISSN: 2162-402X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TRANSFORMING GROWTH FACTOR-BETA-1; CHIMERIC RECEPTOR; ACTIVATION; EXPRESSION; PROTEIN; LOCALIZATION; TGF-BETA-1; IMMUNITY; LYMPHOMAMultiple languages
Oncology; ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/67465

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item