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Decitabine enhances cytotoxic effect of T cells with an anti-CD19 chimeric antigen receptor in treatment of lymphoma

Authors Li S, Xue L, Wang M, Qiang P, Xu H, Zhang X, Kang W, You F, Xu H, Wang Y, Liu X, Yang L, Wang X

Received 23 December 2018

Accepted for publication 26 April 2019

Published 12 July 2019 Volume 2019:12 Pages 5627—5638

DOI https://doi.org/10.2147/OTT.S198567

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Shreya Arora

Peer reviewer comments 2

Editor who approved publication: Dr XuYu Yang


Sujun Li,1,* Lei Xue,2,* Min Wang,3 Ping Qiang,1 Hui Xu,1 Xuhan Zhang,1 Wenyao Kang,3 Fengtao You,3 Hanying Xu,3 Yu Wang,3 Xin Liu,1 Lin Yang,3 Xingbing Wang1,2

1Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 3Department of Quality Assurance, PersonGen-Anke Cellular Therapeutics Co., Ltd, China, Hefei, People’s Republic of China

*These authors contributed equally to this work

Background: CD19-directed chimeric antigen receptor (CAR) T cells have substantial benefit in the treatment of patients with B-cell malignancies. However, despite encouraging therapeutic efficiency, there is limited overall response rate when anti-CD19 CAR-T cells are used to treat patients with relapsed and refractory (R/R) B cell lymphomas. Therefore, it further investigation is urgently needed to improve treatment efficacy.
Method: A combined treatment protocol of CAR-T cell with decitabine (DAC) to treat B cell lymphoma was developed and tested on lymphoma cell lines first, and then efficacy and the underlying mechanism were investigated. After ethical approval was granted, the combined treatment protocol was applied to treat two patients with R/R B-cell lymphomas.
Results: CAR-T cells were prepared successfully, and they recognized CD19 antigen expressed on lymphoma cell lines specifically. Cell-line studies also showed that CD19 antigen expression was increased by DAC pretreatment, and the function of CAR-T cells was not compromised. The cell-line study further demonstrated that lymphoma cells pretreated by DAC responded more to the treatment of CAR-T cells. Two patients with R/R B cell lymphoma were pretreated with DAC then treated with CAR-T, and both achieved complete remission (CR).
Conclusions: The epigenetic modifying drug DAC increases expression of the surface antigen CD19 on lymphoma cells. The DAC pretreatment protocol may lead patients with B cell lymphoma to be more susceptible to adoptive transfer of anti-CD19 CAR-T cells treKeywordsatment.

Keywords: CD19, B cell lymphoma, decitabine (DAC), complete remission, chimeric antigen receptor (CAR) T cells

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