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Oncoimmunology. 2015 May 26;4(11):e1027469. eCollection 2015 Nov.

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

Author information

1
Department of Immunology; Institute of Basic Medicine; School of Life Sciences; Chinese PLA General Hospital ; Beijing, China.
2
Department of Bio-therapeutic; Chinese PLA General Hospital ; Beijing, China.
3
Department of Molecular Biology; Institute of Basic Medicine; School of Life Sciences; Chinese PLA General Hospital ; Beijing, China.
4
Department of Hematology; Chinese PLA General Hospital ; Beijing, China.
5
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.

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.

KEYWORDS:

B-cell acute lymphoblastic leukemia (B-ALL); anti-CD19 chimeric antigen receptor (CAR) T cells; graft-versus-host disease (GVHD); refractory

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