Evaluation of Epstein-Barr virus latent membrane protein 2 specific T-cell receptors driven by T-cell specific promoters using lentiviral vector.
Evaluation of Epstein-Barr virus latent membrane protein 2 specific T-cell receptors driven by T-cell specific promoters using lentiviral vector.
复制标题
使用慢病毒载体评估由 T 细胞特异性启动子驱动的 Epstein-Barr 病毒潜伏膜蛋白 2 特异性 T 细胞受体
DOI：
10.1155/2011/716926
复制
发表时间：
2011
影响因子：
--
通讯作者：
Sun B
中科院分区：
文献类型：
--
作者：
Yang D;Shao Q;Sun H;Mu X;Gao Y;Jiang R;Hou J;Yao K;Chen Y;Sun B
将潜伏膜蛋白2（LMP 2）特异性T细胞受体转导到活化的T淋巴细胞中可以提供一种通用的、MHC限制的方法来在过继免疫疗法中治疗EBV相关肿瘤。我们比较了慢病毒载体中不同来源的TCR特异性启动子，即Vβ6.7、delta、luria和Vβ5.1，以评价人原代外周血单核细胞和T细胞系HSB 2中TCR基因的表达。发现含有Vβ 6.7启动子的载体对于在PBMC中表达是最佳的，并且它们维持转导的TCR的表达长达7周。通过细胞毒性和IFN-γ分泌测定，这些细胞具有识别亚显性EBV潜伏抗原的潜力。在输注慢病毒转导的CTL后，裸鼠也表现出对HLA-A2和LMP 2阳性CNE肿瘤细胞攻击的显著抗性。总之，通过慢病毒转导的LMP 2特异性CTL具有治疗EBV相关肿瘤的潜在用途。
Transduction of latent membrane protein 2 (LMP2)-specific T-cell receptors into activated T lymphocytes may provide a universal, MHC-restricted mean to treat EBV-associated tumors in adoptive immunotherapy. We compared TCR-specific promoters of distinct origin in lentiviral vectors, that is, Vβ6.7, delta, luria, and Vβ5.1 to evaluate TCR gene expression in human primary peripheral blood monocytes and T cell line HSB2. Vectors containing Vβ 6.7 promoter were found to be optimal for expression in PBMCs, and they maintained expression of the transduced TCRs for up to 7 weeks. These cells had the potential to recognize subdominant EBV latency antigens as measured by cytotoxicity and IFN-γ secretion. The nude mice also exhibited significant resistance to the HLA-A2 and LMP2-positive CNE tumor cell challenge after being infused with lentiviral transduced CTLs. In conclusion, LMP2-specific CTLs by lentiviral transduction have the potential use for treatment of EBV-related tumors.