Versatile chimeric antigen receptor platform for controllable and combinatorial T cell therapy.

Autor:	Feldmann A; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany., Hoffmann A; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany., Bergmann R; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary., Koristka S; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany., Berndt N; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany., Arndt C; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany., Rodrigues Loureiro L; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany., Kittel-Boselli E; Tumor Immunology, University Cancer Center (UCC), University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany., Mitwasi N; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany., Kegler A; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany., Lamprecht C; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; Department of Neurology, Center of Clinical Neuroscience, University Hospital Carl Gustav Carus Dresden, Dresden, Germany., González Soto KE; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany., Bachmann M; Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.; Tumor Immunology, University Cancer Center (UCC), University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.; National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; German Cancer Consortium (DKTK), Dresden, Germany.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2020 Jul 03; Vol. 9 (1), pp. 1785608. Date of Electronic Publication: 2020 Jul 03.
DOI:	10.1080/2162402X.2020.1785608
Abstrakt:	Chimeric antigen receptor (CAR) T cells show remarkable therapeutic effects in some hematological malignancies. However, CAR T cells can also cause life-threatening side effects. In order to minimize off-target and on-target/off-tumor reactions, improve safety, enable controllability, provide high flexibility, and increase tumor specificity, we established a novel humanized artificial receptor platform termed RevCARs. RevCAR genes encode for small surface receptors lacking any antigen-binding moiety. Steering of RevCAR T cells occurs via bispecific targeting molecules (TMs). The small size of RevCAR-encoding genes allows the construction of polycistronic vectors. Here, we demonstrate that RevCAR T cells efficiently kill tumor cells, can be steered by TMs, flexibly redirected against multiple targets, and used for combinatorial targeting following the "OR" and "AND" gate logic. (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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