嵌合抗原受体修饰的T细胞治疗急性髓系白血病的临床试验进展

The review in clinical trials of chimeric antigen receptor-modified T cells in the treatment of acute myeloid leukemia

嵌合抗原受体修饰的T细胞(chimeric antigen receptor engineered T cell,CAR-T)治疗是一种靶向过继免疫疗法,CAR-T在治疗急性B淋巴细胞性白血病(B-cell acute lymphoblastic leukemia,B-ALL)的临床实践中已取得良好疗效,目前也被应用于治疗其他血液肿瘤的研究中。过去30年中,急性髓系白血病(acute myeloid leukemia,AML)的标准治疗方案无较大进展,虽然AML患者初次治疗后完全缓解率高,但许多患者最终复发并死亡,因此目前已进行应用CAR-T细胞治疗AML的临床试验,但在治疗过程中仍存在细胞因子释放综合征(cytokine releasing syndrome,CRS)、脱靶效应等毒性作用且疗效并不理想。本文介绍了CAR的结构、CAR-T细胞的采集及制备,并就近5年内CAR-T细胞在治疗AML的临床试验中所取得的进展等方面进行综述。

Chimeric antigen receptor engineered T cell(CAR-T)treatment is a targeted adoptive immunotherapy,which has achieved good results in the clinical practice of B-cell acute lymphoblastic leukemia(B-ALL),and it is currently applied in the treatment of other hematological tumors. In the past three decades,the standard treatment regimen for acute myeloid leukemia(AML)didn′t achieve significant progression. Although AML patients had a high rate of complete remission after initial treatment,many patients still eventually relapse and die. Therefore,clinical trials of CAR-T cells in the treatment of AML have been conducted. However,cytokine releasing syndrome(CRS),off-target effect and other toxic effects still exist in the treatment process,and it was not ideally effective enough to treat the disease. Here,we summarized the structure of CAR,the collection and preparation of CAR-T cells,and reviewed the progression that have made in the clinical trials of CAR-T cells in the treatment of AML in the past five years.