The Outcomes of Epstein-Barr Virus Specific T Cells from Different Sources for EBV Infections in Recipients of Allogeneic Stem Cell Transplantation
Authors: Lin Ren , Huang Fen , Fan Zhiping , Shao Xiaoyan , Dai Guoxian , Xu Na , Xuan Li , Ye Jieyu , Sun Jing , Liu Qifa 
Published: October 2019

Abstract

Background
Epstein-Barr virus (EBV) specific T cells have been proven effective in prevention and treatment of EBV associated-diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the optimal source of EBV specific T cells remains unclear. Here, we compared autologous and donor derived EBV specific T cells with respect to generation ex vivo and the efficacy on EBV infections in the recipients of allo-HSCT.
Methods
Thirty-eight patients with EBV infections were enrolled in this study, including 21 with EBV-emia and 17 with EBV associated post-transplant lymphoproliferative disease (PTLD). EBV specific T cells were generated by immunomagnetic isolation from all the recipients themselves and second-party (original HSCT donor, n=25) or third-party related donors (n=25). The donors were EBV seropositive. The percentages of IFN-γ+ EBV specific T cells in the products and cytotoxic capacity of EBV specific T cells were evaluated.
Results
The median time of EBV infections was 49 days (range, 24-1479 days) post-transplants. The generation of autologous EBV specific T cells failed within 14 days of culture in all the patients because the numbers of cells were insufficient for treatment. Donor derived EBV specific T cells were expanded in vitro for 14 days until the sufficient number (≥ 109) was generated. The percentages of IFN-γ+ EBV specific T cells were comparable in the products generated from second- and third-party donors, but both higher than autologous derived EBV specific T cells. Cytotoxic capacity of EBV specific T cells was lower in autologous EBV specific T cells than donor derived EBV specific T cells. Twenty-one patients with refractory EBV infections (12 with EBV-emia and 9 with PTLD) received EBV specific T cells treatment, including 13 receiving second-party and 8 third-party EBV specific T cells. After treatments, 20 patients exhibited EBV clearance in blood within 6 weeks without recurrence and 1 with PTLD died at 3 weeks after the first infusion of EBV specific T cells with the decline of EBV-DNA copies. Other 8 patients with PTLD received complete remission after treatment. The response rates were not different between the patients receiving second- and third-party donor derived EBV specific T cells. One of the 13 patients with second-party derived EBV specific T cells developed pre-existing chronic graft-versus-host disease (GVHD) exacerbation while 1 developed grade Ⅱ aGVHD in the 8 patients receiving third-party donor derived EBV specific T cells.
Conclusion
The efficacy of EBV-specific T cells derived from second- and third-party are comparable in treatment of EBV infections after allo-HSCT. Autologous derived EBV-specific T cells seems not suitable for treatment because of poor production in vitro.

Disclosures
Fan: National Natural Science Foundation of China (No. 81600141, No. 81770190) and Natural Science Foundation of Guangdong Province (No. 2016A030310390): Research Funding.