Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia.
Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia.
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表达 CD19 嵌合抗原受体的自体或供体来源的 T 细胞在患有髓外白血病的成人 B-ALL 中的耐受性和疗效。
DOI：
10.1080/2162402x.2015.1027469
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发表时间：
2015-11
期刊：
影响因子：
7.2
通讯作者：
Han W
中科院分区：
文献类型：
--
作者：
Dai H;Zhang W;Li X;Han Q;Guo Y;Zhang Y;Wang Y;Wang C;Shi F;Zhang Y;Chen M;Feng K;Wang Q;Zhu H;Fu X;Li S;Han W
T淋巴细胞表达嵌合抗原受体（汽车）的工程化旨在快速建立T细胞介导的肿瘤免疫。在本研究中，我们进行了自体或供体来源的T细胞的初步临床试验，所述T细胞经遗传修饰以表达靶向含有4-1BB和CD 3 β部分的B细胞抗原CD 19的CAR。所有入组患者均患有复发性或化疗难治性B细胞系急性淋巴细胞白血病（B-ALL）。在9名患者中，6名有明确的髓外受累，18周的总生存率为56%。接受预处理化疗的两名患者中的一名实现了三个月的持久完全缓解，髓外病变部分消退。四个没有接受预处理化疗的七名患者取得了显着的回归或混合反应的造血系统和髓外组织为2至9个月。在细胞输注后3-4周接受大量供体来源的抗CD 19 CART（嵌合抗原受体修饰的T）细胞的2例患者中观察到2-3级移植物抗宿主病（GVHD）。这些结果首次表明，供体来源的抗CD 19 CART细胞可引起GVHD和髓外B-ALL的消退。本研究注册为NCT 01864889。
The engineering of T lymphocytes to express chimeric antigen receptors (CARs) aims to establish T cell-mediated tumor immunity rapidly. In this study, we conducted a pilot clinical trial of autologous or donor- derived T cells genetically modified to express a CAR targeting the B-cell antigen CD19 harboring 4-1BB and the CD3ζ moiety. All enrolled patients had relapsed or chemotherapy-refractory B-cell lineage acute lymphocytic leukemia (B-ALL). Of the nine patients, six had definite extramedullary involvement, and the rate of overall survival at 18 weeks was 56%. One of the two patients who received conditioning chemotherapy achieved a three-month durable complete response with partial regression of extramedullary lesions. Four of seven patients who did not receive conditioning chemotherapy achieved dramatic regression or a mixed response in the haematopoietic system and extramedullary tissues for two to nine months. Grade 2–3 graft-versus-host disease (GVHD) was observed in two patients who received substantial donor-derived anti-CD19 CART (chimeric antigen receptor-modified T) cells 3–4 weeks after cell infusions. These results show for the first time that donor-derived anti-CD19 CART cells can cause GVHD and regression of extramedullary B-ALL. This study is registered at as NCT01864889.