| Literature DB >> 25220446 |
Zheng Xiang1, Yinping Liu1, Jian Zheng1, Ming Liu2, Aizhen Lv1, Yulong Gao1, Huaidong Hu3, Kowk-Tai Lam1, Godfrey Chi-Fung Chan1, Yuanzhong Yang4, Honglin Chen5, George Sai-Wah Tsao6, Marc Bonneville7, Yu-Lung Lau1, Wenwei Tu8.
Abstract
Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) after transplantation remains a serious and life-threatening complication. Herein we showed that the aminobisphosphonate pamidronate-expanded human Vγ9Vδ2-T cells efficiently killed EBV-transformed autologous lymphoblastoid B cell lines (EBV-LCL) through γ/δ-TCR and NKG2D receptor triggering and Fas and TRAIL engagement. By inoculation of EBV-LCL in Rag2(-/-)γc(-/-) mice and humanized mice, we established lethal EBV-LPD with characteristics close to those of the human disease. Adoptive transfer of pamidronate-expanded Vγ9Vδ2-T cells alone effectively prevented EBV-LPD in Rag2(-/-)γc(-/-) mice and induced EBV-LPD regression in EBV(+) tumor-bearing Rag2(-/-)γc(-/-) mice. Pamidronate treatment inhibited EBV-LPD development in humanized mice through selective activation and expansion of Vγ9Vδ2-T cells. This study provides proof-of-principle for a therapeutic approach using pamidronate to control EBV-LPD through Vγ9Vδ2-T cell targeting.Entities:
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Year: 2014 PMID： 25220446 DOI： 10.1016/j.ccr.2014.07.026
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743