靶向CD123嵌合抗原受体T细胞治疗急性髓系白血病最新进展

Research progress of T cells expressing CD123 chimeric antigen receptor for treatment of AML

急性髓系白血病(acute myeloid leukemia,AML)是最常见的、死亡率最高的一类白血病。在过去的40年里,尽管人们对于AML的认识更加深入,但是与其他血液肿瘤相比,AML的治疗并没有明显的变化。CD123是AML相关抗原,高表达于白血病干细胞,低或不表达于正常造血干细胞。作为治疗AML的潜在治疗靶点,近期靶向CD123+细胞免疫治疗技术已经有了新的进展,尤其是嵌合抗原受体(chimeric antigen receptor,CAR)T细胞治疗技术发展迅速。早期研究也已经证实CD123 CAR-T细胞具有抗白血病效应,而且对正常造血系统有不同程度的影响,这也为临床治疗复发/难治AML提供了新的思路。

Acute myeloid leukemia （ AML ） is the most c o m m o nacute leukemia in adults and has the highest death rate of allleukemias. Compared with other hematologic malignancies ,there was only a small increment in the 5-year relative overallsurvival for patients with AML in the last 40 years , despite theadvancement in our understanding of AML . C D 123 is an AML -associated antigen that expresses at a high level in leukemic stemcells and leukemic blasts and a low level in normal hematopoieticstem cells. As an attractive surface target for AML therapies ,immune-based therapies targeting C D 123 are being developed recently, especially chimeric antigen receptor（ C A R ） T -cell-basedimmunotherapy. Preclinical data have demonstrated that C D 123C A R-T cells exhibit potent antileukemic activity and various impactson normal hematopoiesis. This will probably be a promisingtreatment for patients with relapsed/refractory AML .