Generation of Chimeric Antigen Receptors against Tetraspanin 7.

Autor: Pieper T; Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, Germany., Roth KDR; Institut für Biochemie, Biotechnologie und Bioinformatik, Abteilung Medizinische Biotechnologie, Technische Universität Braunschweig, 38106 Braunschweig, Germany., Glaser V; Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, Germany., Riet T; Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, Germany.; Department I of Internal Medicine, Tumor Genetics, University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50933 Cologne, Germany., Buitrago-Molina LE; Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, Germany., Hagedorn M; Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, Germany., Lieber M; Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, Germany., Hust M; Institut für Biochemie, Biotechnologie und Bioinformatik, Abteilung Medizinische Biotechnologie, Technische Universität Braunschweig, 38106 Braunschweig, Germany., Noyan F; Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, Germany., Jaeckel E; Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, Germany.; Department of Liver Transplantation, Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, ON M5T 0S8, Canada., Hardtke-Wolenski M; Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, Germany.; Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, 47057 Essen, Germany.
Jazyk: angličtina
Zdroj: Cells [Cells] 2023 May 23; Vol. 12 (11). Date of Electronic Publication: 2023 May 23.
DOI: 10.3390/cells12111453
Abstrakt: Adoptive transfer of antigen-specific regulatory T cells (Tregs) has shown promising results in the treatment of autoimmune diseases; however, the use of polyspecific Tregs has limited effects. However, obtaining a sufficient number of antigen-specific Tregs from patients with autoimmune disorders remains challenging. Chimeric antigen receptors (CARs) provide an alternative source of T cells for novel immunotherapies that redirect T cells independently of the MHC. In this study, we aimed to generate antibody-like single-chain variable fragments (scFv) and subsequent CARs against tetraspanin 7 (TSPAN7), a membrane protein highly expressed on the surface of pancreatic beta cells, using phage display technology. We established two methods for generating scFvs against TSPAN7 and other target structures. Moreover, we established novel assays to analyze and quantify their binding abilities. The resulting CARs were functional and activated specifically by the target structure, but could not recognize TSPAN7 on the surface of beta cells. Despite this, this study demonstrates that CAR technology is a powerful tool for generating antigen-specific T cells and provides new approaches for generating functional CARs.
Databáze: MEDLINE
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