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

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. [Display omitted] •CD37 is expressed on AML blasts•CD37 expression correlates with ELN 2017 risk stratification•CD37CAR T cells are efficient against AML in vitro and in vivo•CD37CAR T cells do not deplete myeloid progenitors Caulier et al. demonstrate that CD37, a B cell marker, is expressed on the cell surface of the majority of primary AML samples. A CAR construct directed against CD37 controls AML progression, suggesting that CD37CAR T cells represent a promising solution for AML treatment.