期刊
ONCOIMMUNOLOGY
卷 4, 期 11, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2015.1027469
关键词
anti-CD19 chimeric antigen receptor (CAR) T cells; B-cell acute lymphoblastic leukemia (B-ALL); graft-versus-host disease (GVHD); refractory
资金
- National Natural Science Foundation of China [31270820, 81230061, 81121004]
- Beijing Nova Program [Z141107001814104]
- National Basic Science and Development Programme of China [2012CB518103, 2012AA020502, 2013BAI01B00]
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.
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