Engineering CAR-T cells for radiohapten capture in imaging and radioimmunotherapy applications.

Autor:	Kurtz K; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA., Eibler L; Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Dacek MM; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA., Carter LM; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Veach DR; Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA., Lovibond S; Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Reynaud E; Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Qureshy S; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., McDevitt MR; Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA., Bourne C; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Immunology and Microbial Pathogenesis Program, Weill Cornell Medical College, New York, NY 10065, USA., Monette S; Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and The Rockefeller University, New York, NY 10065, USA., Punzalan B; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Khayat S; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA., Verma S; Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA., Kesner AL; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Cheung NV; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Schöder H; Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA., Gajecki L; Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Cheal SM; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA., Larson SM; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA., Scheinberg DA; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA., Krebs S; Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA.
Jazyk:	angličtina
Zdroj:	Theranostics [Theranostics] 2023 Oct 08; Vol. 13 (15), pp. 5469-5482. Date of Electronic Publication: 2023 Oct 08 (Print Publication: 2023).
DOI:	10.7150/thno.87489
Abstrakt:	Rationale: The in vivo dynamics of CAR-T cells remain incompletely understood. Novel methods are urgently needed to longitudinally monitor transferred cells non-invasively for biodistribution, functionality, proliferation, and persistence in vivo and for improving their cytotoxic potency in case of treatment failure. Methods: Here we engineered CD19 CAR-T cells ("Thor"-cells) to express a membrane-bound scFv, huC825, that binds DOTA-haptens with picomolar affinity suitable for labeling with imaging or therapeutic radionuclides. We assess its versatile utility for serial tracking studies with PET and delivery of α-radionuclides to enhance anti-tumor killing efficacy in sub-optimal adoptive cell transfer in vivo using Thor-cells in lymphoma models. Results: We show that this reporter gene/probe platform enables repeated, sensitive, and specific assessment of the infused Thor-cells in the whole-body using PET/CT imaging with exceptionally high contrast. The uptake on PET correlates with the Thor-cells on a cellular and functional level. Furthermore, we report the ability of Thor-cells to accumulate cytotoxic alpha-emitting radionuclides preferentially at tumor sites, thus increasing therapeutic potency. Conclusion: Thor-cells are a new theranostic agent that may provide crucial information for better and safer clinical protocols of adoptive T cell therapies, as well as accelerated development strategies. Competing Interests: Competing Interests: MSK has filed for patent protection on behalf of M.M.D., D.R.V., M.R.M., N.K.C., S.M.C., S.M.L., D.A.S., and S.K. for inventions related to the work described in this paper. S.M.C. was named as an inventor on multiple patents filed by MSK, including those licensed to Y-mAbs Therapeutics. N.K.C. has a financial interest in Abpro-Labs, Biotec Pharmacon, Eureka Therapeutics, and Y-mAbs Therapeutics that may work in areas related to this paper. D.A.S. is an advisor to, or owns equity in, IOVA, ATNM, LNTH, Eureka Therapeutics, CoImmune, Atengen, Repertoire, and PFE, which may work in areas related to this paper. S.M.L. reports receiving commercial research grants from Y-mAbs Therapeutics, Genentech, Inc., WILEX AG, Telix Pharmaceuticals Limited, and Regeneron Pharmaceuticals, Inc.; holding ownership interest/equity in Voreyda Theranostics Inc. and Elucida Oncology Inc., and holding stock in Y-mAbs Therapeutics. S.M.L. is the inventor and owner of issued patents both currently unlicensed and licensed by MSK to Samus Therapeutics, Inc., Y-mAbs Therapeutics Inc., and Elucida Oncology, Inc.; is or has served as a consultant to Cynvec LLC, Eli Lilly & Co., Prescient Therapeutics Limited, Advanced Innovative Partners, LLC, Gerson Lehrman Group, Progenics Pharmaceuticals, Inc., and Janssen Pharmaceuticals, Inc. SK has consulted for Telix Pharmaceuticals Ltd. and acknowledges support for investigator services from RayzeBio. The remaining authors report no competing interests. (© The author(s).)
Databáze:	MEDLINE
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