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... - 中国病毒学论坛|我们一直在坚持！

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.

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4-1BB和CD3ζ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和髓外B-ALL的缓解。