TY - JOUR
T1 - CD37 in acute myeloid leukemia
T2 - a novel surface target for drug delivery
AU - Jeremy, Erin
AU - Artiga, Esthela
AU - Elgamal, Sara
AU - Cheney, Carolyn
AU - Eicher, Dalen
AU - Zalponik, Kevan
AU - Orwick, Shelley
AU - Mao, Charlene
AU - Wasmuth, Ronni
AU - Harrington, Bonnie
AU - Mustonen, Allison
AU - Beshay, Peter
AU - Halley, Patrick
AU - Castro, Carlos
AU - Williams, Katie
AU - Hing, Zachary
AU - Chen, Timothy
AU - Lucas, Christopher
AU - Vantangoli, Nicholas J.
AU - Lapalombella, Rosa
AU - Grieselhuber, Nicole
AU - Mo, Xiaokui
AU - Hertlein, Erin
AU - Muthusamy, Natarajan
AU - Mundy-Bosse, Bethany L.
AU - Byrd, John C.
AU - Larkin, Karilyn T.
N1 - Publisher Copyright:
© 2024 by The American Society of Hematology.
PY - 2025/1/14
Y1 - 2025/1/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85215263294&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2024013590
DO - 10.1182/bloodadvances.2024013590
M3 - Article
C2 - 39348689
AN - SCOPUS:85215263294
SN - 2473-9529
VL - 9
SP - 1
EP - 14
JO - Blood Advances
JF - Blood Advances
IS - 1
ER -