Mucin-1-Targeted Chimeric Antigen Receptor T Cells Are Effective and Safe in Controlling Solid Tumors in Immunocompetent Host.

Autor:	Zhou R; Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC., Wu ST; Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC.; Medpace, Irving, TX., Yazdanifar M; Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC.; Adaptive Biotechnologies, South San Francisco, CA., Williams C; Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC.; Pfizer, Cambridge, MA., Sanders A; Department of Bioinformatics, University of North Carolina at Charlotte, Charlotte, NC., Brouwer C; Department of Bioinformatics, University of North Carolina at Charlotte, Charlotte, NC., Maher J; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, London, UK., Mukherjee P; Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC.
Jazyk:	angličtina
Zdroj:	Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2024 Apr 01; Vol. 47 (3), pp. 77-88. Date of Electronic Publication: 2024 Jan 25.
DOI:	10.1097/CJI.0000000000000505
Abstrakt:	The chimeric antigen receptor (CAR) T-cell therapy in solid epithelial tumors has been explored, however, with limited success. As much of the preclinical work has relied on xenograft models in immunocompromised animals, the immune-related efficacies and toxicities may have been missed. In this study, we engineered syngeneic murine CAR T cells targeting the tumor form of human mucin-1 (tMUC1) and tested the MUC1 CAR T cells' efficacy and toxicity in the immunocompetent human MUC1-expressing mouse models. The MUC1 CAR T cells significantly eliminated murine pancreatic and breast cancer cell lines in vitro. In vivo, MUC1 CAR T cells significantly slowed the mammary gland tumor progression in the spontaneous PyVMT×MUC1.Tg (MMT) mice, prevented lung metastasis, and prolonged survival. Most importantly, there was minimal short or long-term toxicity with acceptable levels of transient liver toxicity but no kidney toxicity. In addition, the mice did not show any signs of weight loss or other behavioral changes with the treatment. We also report that a single dose of MUC1 CAR T-cell treatment modestly reduced the pancreatic tumor burden in a syngeneic orthotopic model of pancreatic ductal adenocarcinoma given at late stage of an established tumor. Taken together, these findings suggested the further development of tMUC1-targeted CAR T cells as an effective and relatively safe treatment modality for various tMUC1-expressing solid tumors. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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