State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin.
Central Laboratory, Ganzhou Key Laboratory of Molecular Medicine, the Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China.
J Immunother. 2022;45(2):67-77. doi: 10.1097/CJI.0000000000000406.
The relapsed and refractory acute myeloid leukemia (AML) patients receiving traditional chemotherapies have poor survival rate. Chimeric antigen receptor (CAR)-modified T cells have demonstrated remarkable effectiveness against some malignancies. However, most of CAR-Ts targeting the candidate proteins on AML cells induce hematopoietic cell suppression. Because of extensive heterogeneity among different types of AML, it is essential to expand the choice of target antigen for the CAR-T treatment of AML. CD64 (FcγRI) is a transmembrane protein with broad expression on various types of AML cells, especially monocytic AML cells, but it is absent on hematopoietic stem cells (HSCs) and most of nonmonocytes. Here, we found that some types of AML patients showed the homogeneous high-level expression of CD64. So, we created a CAR-T targeting CD64 (64bbz) and further verified its high efficiency for eradicating CD64+AML cells. In addition, 64bbz showed no cytotoxicity to HSCs. Overall, we developed a new treatment option for AML by using CD64 CAR-T cells while avoiding ablation of HSCs.
接受传统化疗的复发/难治性急性髓系白血病（AML）患者的生存率较差。嵌合抗原受体（CAR）修饰的 T 细胞已被证明对某些恶性肿瘤具有显著疗效。然而，大多数针对 AML 细胞候选蛋白的 CAR-T 会诱导造血细胞抑制。由于不同类型的 AML 之间存在广泛的异质性，因此扩大 CAR-T 治疗 AML 的靶抗原选择至关重要。CD64（FcγRI）是一种跨膜蛋白，在各种类型的 AML 细胞上广泛表达，尤其是单核细胞性 AML 细胞，但在造血干细胞（HSCs）和大多数非单核细胞上不存在。在这里，我们发现一些类型的 AML 患者表现出 CD64 的同质高水平表达。因此，我们构建了一种靶向 CD64 的 CAR-T（64bbz），并进一步验证了其清除 CD64+AML 细胞的高效性。此外，64bbz 对 HSCs 没有细胞毒性。总之，我们通过使用 CD64 CAR-T 细胞为 AML 开发了一种新的治疗选择，同时避免了 HSCs 的消融。
