CD37 is a safe chimeric antigen receptor target to treat acute myeloid leukemia.

Autor:	Caulier B; Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway; Institute for Cancer Research, Department of Molecular Cell Biology, Oslo University Hospital, Oslo, Norway; Center for Cancer Cell Reprogramming (CanCell), Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Joaquina S; Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway., Gelebart P; Department of Clinical Science, Precision Oncology Research Group, University of Bergen, 5021 Bergen, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway., Dowling TH; Department of Clinical Science, Precision Oncology Research Group, University of Bergen, 5021 Bergen, Norway; Centre for Pharmacy, Department of Clinical Science, University of Bergen, Bergen, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway., Kaveh F; Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway., Thomas M; Institue of AI for Health, Helmholtz Munich, 85764 Neuherberg, Germany; School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany., Tandaric L; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway., Wernhoff P; Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway., Katyayini NU; Institute for Cancer Research, Department of Molecular Cell Biology, Oslo University Hospital, Oslo, Norway; Center for Cancer Cell Reprogramming (CanCell), Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Wogsland C; Department of Clinical Science, Precision Oncology Research Group, University of Bergen, 5021 Bergen, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway., Gjerstad ME; Department of Clinical Science, Precision Oncology Research Group, University of Bergen, 5021 Bergen, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway., Fløisand Y; Institute for Cancer Research, Department of Molecular Cell Biology, Oslo University Hospital, Oslo, Norway., Kvalheim G; Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway., Marr C; Institue of AI for Health, Helmholtz Munich, 85764 Neuherberg, Germany., Kobold S; Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany; German Center for Translational Cancer Research (DKTK), Partner Site Munich, Munich, Germany; Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München, Research Center for Environmental Health (HMGU), Neuherberg, Germany., Enserink JM; Institute for Cancer Research, Department of Molecular Cell Biology, Oslo University Hospital, Oslo, Norway; Center for Cancer Cell Reprogramming (CanCell), Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Section for Biochemistry and Molecular Biology, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway., Gjertsen BT; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway., McCormack E; Department of Clinical Science, Precision Oncology Research Group, University of Bergen, 5021 Bergen, Norway; Centre for Pharmacy, Department of Clinical Science, University of Bergen, Bergen, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway., Inderberg EM; Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway., Wälchli S; Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway. Electronic address: sebastw@rr-research.no.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Jun 18; Vol. 5 (6), pp. 101572. Date of Electronic Publication: 2024 May 15.
DOI:	10.1016/j.xcrm.2024.101572
Abstrakt:	Acute myeloid leukemia (AML) is characterized by the accumulation of immature myeloid cells in the bone marrow and the peripheral blood. Nearly half of the AML patients relapse after standard induction therapy, and new forms of therapy are urgently needed. Chimeric antigen receptor (CAR) T therapy has so far not been successful in AML due to lack of efficacy and safety. Indeed, the most attractive antigen targets are stem cell markers such as CD33 or CD123. We demonstrate that CD37, a mature B cell marker, is expressed in AML samples, and its presence correlates with the European LeukemiaNet (ELN) 2017 risk stratification. We repurpose the anti-lymphoma CD37CAR for the treatment of AML and show that CD37CAR T cells specifically kill AML cells, secrete proinflammatory cytokines, and control cancer progression in vivo. Importantly, CD37CAR T cells display no toxicity toward hematopoietic stem cells. Thus, CD37 is a promising and safe CAR T cell AML target. Competing Interests: Declaration of interests The CD37CAR construct has been patented (WO2017118745A1) and E.M.I., G.K., and S.W. are listed among the inventors. S.K. has received honoraria from TCR2 Inc., Miltenyi, Novartis, BMS, and GSK. S.K. is inventor of several patents in the field of immuno-oncology. S.K. received license fees from TCR2 Inc. and Carina Biotech. S.K. received research support from TCR2 Inc., Plectonic GmBH, Tabby Therapeutics, and Arcus Bioscience for work unrelated to this manuscript. The funding agencies had no role in the conduction and management of the presented research and were not involved in the preparation of this manuscript. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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