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

Benjamin Caulier; Sandy Joaquina; Pascal Gelebart; Tara Helén Dowling; Fatemeh Kaveh; Moritz Thomas; Luka Tandaric; Patrik Wernhoff; Niveditha Umesh Katyayini; Cara Wogsland; May Eriksen Gjerstad; Yngvar Fløisand; Gunnar Kvalheim; Carsten Marr; Sebastian Kobold; Jorrit M Enserink; Bjørn Tore Gjertsen; Emmet McCormack; Else Marit Inderberg; Sébastien Wälchli

doi:10.1016/j.xcrm.2024.101572

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

Cell Rep Med. 2024 May 8:101572. doi: 10.1016/j.xcrm.2024.101572. Online ahead of print.

Authors

Benjamin Caulier¹, Sandy Joaquina², Pascal Gelebart³, Tara Helén Dowling⁴, Fatemeh Kaveh², Moritz Thomas⁵, Luka Tandaric⁶, Patrik Wernhoff², Niveditha Umesh Katyayini⁷, Cara Wogsland³, May Eriksen Gjerstad³, Yngvar Fløisand⁸, Gunnar Kvalheim², Carsten Marr⁹, Sebastian Kobold¹⁰, Jorrit M Enserink¹¹, Bjørn Tore Gjertsen¹², Emmet McCormack⁴, Else Marit Inderberg², Sébastien Wälchli¹³

Affiliations

¹ 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.
² Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway.
³ Department of Clinical Science, Precision Oncology Research Group, University of Bergen, 5021 Bergen, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway.
⁴ 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.
⁵ Institue of AI for Health, Helmholtz Munich, 85764 Neuherberg, Germany; School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
⁶ Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
⁷ 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.
⁸ Institute for Cancer Research, Department of Molecular Cell Biology, Oslo University Hospital, Oslo, Norway.
⁹ Institue of AI for Health, Helmholtz Munich, 85764 Neuherberg, Germany.
¹⁰ 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.
¹¹ 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.
¹² Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.
¹³ Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway. Electronic address: sebastw@rr-research.no.

PMID: 38754420
DOI: 10.1016/j.xcrm.2024.101572

Abstract

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.

Keywords: AML; CAR T cell; CD37; acute myeloid leukemia; chimeric antigen receptor; hematopoietic stem cell; immunotherapy; patient-derived xenograft.