1. CD37 in acute myeloid leukemia: a novel surface target for drug delivery.
- Author
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Jeremy E, Artiga E, Elgamal S, Cheney C, Eicher D, Zalponik K, Orwick S, Mao C, Wasmuth R, Harrington B, Mustonen A, Beshay P, Halley P, Castro C, Williams K, Hing Z, Chen T, Lucas C, Vantangoli NJ, Lapalombella R, Grieselhuber N, Mo X, Hertlein E, Muthusamy N, Mundy-Bosse BL, Byrd JC, and Larkin KT
- Subjects
- Humans, Mice, Animals, Drug Delivery Systems, Antigens, Neoplasm metabolism, Xenograft Model Antitumor Assays, Cell Line, Tumor, Molecular Targeted Therapy, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute pathology, Tetraspanins metabolism, Immunoconjugates therapeutic use, Immunoconjugates pharmacology
- Abstract
Abstract: 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., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2025
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