PDF(Pubmed)
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.
摘要：
急性髓性白血病（AML）的特征是骨髓和外周血中未成熟骨髓细胞的积累。近一半的AML患者在标准诱导治疗后复发，迫切需要新的治疗形式。由于缺乏疗效和安全性，嵌合抗原受体（CAR）T疗法迄今在AML中尚未成功。的确,最有吸引力的抗原靶标是干细胞标志物，如CD33或CD123。我们证明了CD37，一种成熟的B细胞标志物，在AML样本中表达，其存在与欧洲白血病网(ELN)2017年风险分层相关。我们将抗淋巴瘤CD37CAR重新用于治疗AML，并显示CD37CART细胞特异性杀死AML细胞，分泌促炎细胞因子，并在体内控制癌症进展。重要的是,CD37CART细胞对造血干细胞没有毒性。因此，CD37是一种有前途且安全的CAR-T细胞AML靶标。
