title: 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. This study is registered at www.clinicaltrials.gov as NCT01864889.
authors.affiliation: Department of Immunology; Institute of Basic Medicine; School of Life Sciences; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Hanren
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Bio-therapeutic; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biology; Institute of Basic Medicine; School of Life Sciences; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Immunology; Institute of Basic Medicine; School of Life Sciences; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Qingwang
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Immunology; Institute of Basic Medicine; School of Life Sciences; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Yelei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Bio-therapeutic; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology; Institute of Basic Medicine; School of Life Sciences; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Bio-therapeutic; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Chunmeng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Bio-therapeutic; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Bio-therapeutic; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Bio-therapeutic; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Meixia
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Bio-therapeutic; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Kaichao
authors.initials: K
authors.lastname: Feng
authors.affiliation: Department of Hematology; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Quanshun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Hematology; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Bio-therapeutic; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Hematology; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Immunology; Institute of Basic Medicine; School of Life Sciences; Chinese PLA General Hospital ; Beijing, China ; Department of Bio-therapeutic; Chinese PLA General Hospital ; Beijing, China ; Department of Molecular Biology; Institute of Basic Medicine; School of Life Sciences; Chinese PLA General Hospital ; Beijing, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
keywords: B-cell acute lymphoblastic leukemia (B-ALL); anti-CD19 chimeric antigen receptor (CAR) T cells; graft-versus-host disease (GVHD); refractory