CD37 in acute myeloid leukemia: a novel surface target for drug delivery
Acute myeloid leukemia (AML) is the most common and lethal leukemia in adults. AML consists of many genetic subtypes, which limits broad applicability of targeted therapy. We discovered that the hematopoiesis-restricted tetraspanin CD37 is expressed on the majority of primary AML blasts and thus may represent a common therapeutic target for AML regardless of subtype. We demonstrate that the internalization properties of CD37 are distinct in AML blasts when compared with normal blood cells, and that CD37 rapidly accumulates inside AML blasts via dynamin-dependent endocytosis. Our work revealed that the clinically relevant anti-CD37 antibody-drug conjugate (ADC) Debio 1562 (αCD37-DM1) is highly cytotoxic to AML blasts, but not normal hematopoietic stem cells. We found that αCD37-DM1 improved clinical outcomes and overall survival in multiple in vivo models of AML. Together, these data demonstrate that targeting CD37 with an ADC such as αCD37-DM1 is a feasible and promising therapeutic option for the treatment of AML.
Authors
- Nicole R. Grieselhuber (ORCID: https://orcid.org/0000-0003-3495-5932)
- Bethany L. Mundy-Bosse (ORCID: https://orcid.org/0009-0004-7397-7653)
- Natarajan Muthusamy (ORCID: https://orcid.org/0000-0002-0351-4504)
- Xiaokui Molly Mo (ORCID: https://orcid.org/0000-0002-9797-2687)
- Rosa Lapalombella (ORCID: https://orcid.org/0000-0001-6916-9400)
- Patrick D. Halley (ORCID: https://orcid.org/0000-0003-4942-8908)
- Erin Hertlein (ORCID: https://orcid.org/0000-0001-8493-5679)
- Peter E. Beshay (ORCID: https://orcid.org/0000-0003-2191-8219)
- Sara Elgamal (ORCID: https://orcid.org/0000-0003-2274-9891)
- Katie Williams (ORCID: https://orcid.org/0000-0002-8252-8196)
- Shelley Orwick (ORCID: https://orcid.org/0000-0002-4537-1409)
- Erin G. Jeremy (ORCID: https://orcid.org/0000-0002-5803-5885)
- Esthela Artiga
- Bonnie K. Harrington (ORCID: https://orcid.org/0000-0003-2658-6188)
- Hsiaoyin Mao
- Timothy L. Chen (ORCID: https://orcid.org/0000-0002-2704-4105)
- Christopher R. Lucas (ORCID: https://orcid.org/0000-0002-4296-8656)
- John C. Byrd (ORCID: https://orcid.org/0000-0002-8778-1000)
- Zachary A. Hing
- Nicholas J. Vantangoli (ORCID: https://orcid.org/0000-0001-8003-9236)
- Carolyn Cheney (ORCID: https://orcid.org/0000-0001-9697-7585)
- Karilyn Larkin (ORCID: https://orcid.org/0000-0002-1898-9836)
- Carlos E. Castro (ORCID: https://orcid.org/0000-0001-7023-6105)
- Allison Mustonen
- Kevan Zalponik
- Ronni Wasmuth
- Dalen Eicher
Institutions
- The Ohio State University Wexner Medical Center (US)
- California University of Pennsylvania (US)
- The Ohio State University (US)
- University of Cincinnati (US)
- University of Pennsylvania (US)
- Michigan State University (US)
- Philadelphia University (US)
Publication Details
- Journal
- Blood Advances
- Published
- 2024-09-30
- DOI
- https://doi.org/10.1182/bloodadvances.2024013590
- Citations
- 4
- Primary Topic
- Blood disorders and treatments
- Type
- article
- Field-Weighted Citation Impact
- 2.20
Funders
- Ohio State University