Selective expansion and enhanced anti-tumor effect of antigen-specific CD4^(+)T cells by retrovirus-mediated IL-15 expression  

作　　者：Jizhou Lv Ning Tao Hao Wu Xiaoman Liu Xia Xu Yingxin Xu Zhihai Qin 

机构地区：[1]National Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Science,Beijing 100101,China [2]Graduate School of Chinese Academy of Sciences,Beijing 100080,China [3]Department of Interventional Ultrasound,Chinese PLA General Hospital,Beijing 100853,China

出　　处：《Protein & Cell》2011年第7期585-599,共15页蛋白质与细胞（英文版）

基　　金：supported by the National Basic Research Program(973 Program)(No.2006CB504304);the National Programs for High Technology Research and Development Program(863 Program)(No.2006AA02Z4B9).

摘　　要：Mounting evidence has demonstrated that CD4^(+)T cells play an important role in anti-tumor immune responses.Thus,adoptive transfer of these cells may have great potential for anti-cancer therapy.However,due to the difficulty to generate sufficient tumor-specific CD4^(+)T cells,the use of CD4^(+)T cells in tumor therapy is limited.It has been found that IL-15 transfection enhances the proliferation and anti-tumor activity of tumor-specific CD8+Tcells,but the effect of IL-15 transfection on CD4^(+)T cells remains unknown.Here,the effects of retrovirusmediated IL-15 expression in Ova-specific CD4^(+)T cells from Do11.10 mice were evaluated and it was discovered that IL-15 transfected CD4^(+)T cells expressed both soluble and membrane-bound IL-15.Retrovirusmediated IL-15 expression led to a selective expansion of antigen-specific CD4^(+)T cells by inhibiting their apoptosis.In vivo IL-15 transfected CD4^(+)T cells were more effective in suppressing tumor growth than control retroviral vector transfected ones.To ensure the safety of the method,the employment of thymidine kinase gene made it possible to eliminate these transgenic CD4^(+)T cells following ganciclovir treatment.Together,we show that IL-15 transfection induced a selective expansion of antigen-specific CD4^(+)T cells ex vivo and enhanced their tumor-suppression effects in vivo.This has an important significance for improving the efficacy of adoptive T cell therapy.

关 键 词：CD4^(+)T cells retrovirus vector IL-15 tumor therapy 

分 类 号：R73[医药卫生—肿瘤]