Effiefficacy and safety of allogeneic CD123 CAR-NK cell therapy in Relapsed/Refractory Acute Myeloid Leukemia

作者：Wei Mu, A. H. Zhang, Xingcheng Yang, Xiaoxi Zhou, Jie Zhao, Yicheng Zhang, Wei-Wei Tian, Junjie Shen, Haoyue Qin, Yingzi Zhang, Cheng Qian, Jia Wei · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-1639 · 被引用次数：3 · 研究领域：Immune Cell Function and Interaction、CAR-T cell therapy research、Lymphoma Diagnosis and Treatment

Abstract Background: While CAR-T cell therapy has revolutionized the treatment of certain hematologic malignancies, including B-cell malignancies and multiple myeloma, its application in R/R AML presents distinct and formidable challenges, including target antigen heterogeneity, immunosuppressive microenvironments, and treatment-related toxicities such as CRS and neurotoxicity. NK cells, with their inherent tumor-killing mechanisms, favorable safety profile, and potential for 'off-the-shelf’ allogeneic use, offer a compelling alternative. The high and consistent expression of CD123 on AML blast cells and leukemia stem cells further positions CD123-directed CAR-NK therapy as a promising novel approach. In this study, we developed a novel CD123 CAR-NK product using NK cells instead of T cells, aiming to evaluate its safety, antitumor activity, and optimal dosing in patients with R/R AML, and to explore strategies to further enhance its therapeutic efficacy. Patients and methods: A fully human-derived CD123-targeting CAR-NK cell therapy was developed and validated preclinically. CD123 CAR-NK cells were generated via lentiviral transduction using PBMCs from a single donor and cryopreserved for clinical use. Five eligible adult patients (aged 18–75 years) with R/R AML were enrolled and treated with escalating doses of CD123 CAR-NK cells. All patients had undergone extensive prior therapies. Two patients had previously failed allogeneic HSCT. Prior to CAR-NK cell infusion, patients...