Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia

被引：179

作者：

Dai, Hanren ^{[1
]}

Zhang, Wenying ^{[2
]}

Li, Xiaolei ^{[3
]}

Han, Qingwang ^{[1
]}

Guo, Yelei ^{[1
]}

Zhang, Yajing ^{[2
]}

Wang, Yao ^{[1
]}

Wang, Chunmeng ^{[2
]}

Shi, Fengxia ^{[2
]}

Zhang, Yan ^{[2
]}

Chen, Meixia ^{[2
]}

Feng, Kaichao ^{[2
]}

Wang, Quanshun ^{[4
]}

Zhu, Hongli ^{[4
]}

Fu, Xiaobing ^{[2
]}

Li, Suxia ^{[4
]}

Han, Weidong ^{[1
,2
,3
]}

机构：

[1] Chinese Peoples Liberat Army Gen Hosp, Sch Life Sci, Inst Basic Med, Dept Immunol, Beijing, Peoples R China

[2] Chinese Peoples Liberat Army Gen Hosp, Dept Biotherapeut, Beijing, Peoples R China

[3] Chinese Peoples Liberat Army Gen Hosp, Sch Life Sci, Inst Basic Med, Dept Mol Biol, Beijing, Peoples R China

[4] Chinese Peoples Liberat Army Gen Hosp, Dept Hematol, Beijing, Peoples R China

来源：

ONCOIMMUNOLOGY | 2015年 / 4卷 / 11期

基金：

中国国家自然科学基金;

关键词：

anti-CD19 chimeric antigen receptor (CAR) T cells; B-cell acute lymphoblastic leukemia (B-ALL); graft-versus-host disease (GVHD); refractory; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; BONE-MARROW; MYELOID-LEUKEMIA; METASTATIC MELANOMA; IMATINIB MESYLATE; CANCER REGRESSION; LINEAGE LEUKEMIA; POOR-PROGNOSIS; CLINICAL-TRIAL;

D O I：

10.1080/2162402X.2015.1027469

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 CD3 zeta 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.

引用

页数：12

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