急性髓系白血病 (AML) 是急性白血病的一种常见类型，当前可用的治疗方法并不理想。在本研究中，我们报道了一种采用基因改造的双功能CAR-NK细胞的免疫细胞治疗策略。这些细胞通过CD33分子高效靶向AML细胞，并通过表达和胞外分泌抗CD16抗体 (B16) 刺激NK细胞介导的细胞毒性。抗体通过结合NK细胞的Fc受体，使得细胞具有双重功能。与仅靶向CD33的CAR-NK细胞相比，双功能CD33/B16 CAR-NK细胞在体外对AML细胞的杀伤效率更高。其效率增加了约4倍，根据需要实现80%杀伤活性所需细胞数来确定。一个采用异种移植模型的体内研究也揭示了白血病细胞的有效清除和更长的存活时间，至少可以达到60天没有复发或死亡。另外，根据细胞因子释放检测，CAR-NK细胞的安全性并没有因另外表达B16而改变。这些数据揭示了一种有前途的CAR-NK治疗方法，可用于治疗AML患者，这可能有助于改善CAR-NK基于治疗策略，同时也有潜力用于治疗其他肿瘤。版权所有 © 2023 Elsevier B.V.

Acute myeloid leukemia (AML) is a common form of acute leukemia, and the currently available treatments are unsatisfactory. In the present study, we report an immune cell therapeutic strategy that employed genetically modified bifunctional CAR-NK cells. These cells combined the efficient targeting of AML cells by the CD33 molecule with the concomitant stimulation of NK cell-mediated cytotoxicity via the expression and extracellular secretion of anti-CD16 antibody (B16) that binds back to the FC receptor of NK cells. Compared to CAR-NK cells that target CD33 only, the bifunctional CD33/B16 CAR-NK cells showed superior killing efficiency toward AML cells in vitro. The increase in efficiency was approximately four-fold, as determined based on the number of cells needed to achieve 80% killing activity. An in vivo study using a xenograft model also revealed the effective clearance of leukemic cells and much longer survival, with no relapse or death for at least 60 days. In addition, the safety of CAR-NK cells did not change with additional expression of B16, as determined by the release of cytokines. These data revealed the development of a promising CAR-NK approach for the treatment of patients with AML, which may improve CAR-NK-based treatment strategy in general and may potentially be used to treat other tumors as well.Copyright © 2023 Elsevier B.V. All rights reserved.