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自体或供体CD19 CAR-T细胞对成人B细胞急性淋巴细胞髓外白血病的耐受性和有效性

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发表于 2015-12-13 19:43:34 | 显示全部楼层 |阅读模式
Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia.
Abstract
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.
自体或供体CD19 CAR-T细胞对成人B细胞急性淋巴细胞髓外白血病的耐受性和有效性
摘要
T淋巴细胞改造后表达嵌合抗原受体(CARs),目标是快速建立T 细胞为基础的肿瘤免疫治疗。在这个研究中,我们建立了一个临床试验,使用自体或供体来源的T细胞,经过修改后表达B细胞靶向抗原CD19,并且含有4-1BBCD3ζ衍生部分。所有入选者是复发或化疗难治性B细胞急性淋巴细胞白血病(ALL患者。在九例患者中,六人有明确的髓外受累,总体生存率在18周时为56%两个患者中的一个接受调理化疗取得了3个月的持久的完全缓解与髓外病变局部的回归。七个患者中的四个没有接受化疗,但取得了明显的缓解,或者说在造血系统和髓外组织两个月到九个月间都有效果。注射充足的CAR-T细胞后的3-4周之后,2个患者观察到了2-3级的移植物抗宿主病。这些结果第一次表明,供体来源的抗CD19细胞可以导致GVHD髓外B-ALL的缓解。
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