WT1多肽特异性T细胞受体基因转导正常T细胞的抗肺癌效应  

Cytotoxicity of T cells transduced with WT1 peptide-specific T-cell receptor gene against human lung cancer cells in vitro

作　　者：安军[1] 蔡松旺[1] 李昀[1] 张军航[1] 

机构地区：[1]中山大学附属第三医院胸心外科,广东广州510630

出　　处：《南方医科大学学报》2014年第9期1319-1323,共5页Journal of Southern Medical University

基　　金：留学回国人员科研启动基金

摘　　要：目的通过基因转导技术获得WT1多肽特异性TCR基因转导的正常外周CD8+T细胞,检测其对肺癌细胞的杀伤活性,探讨TCR基因转导用于过继性细胞治疗肺癌的可行性及安全性。方法通过克隆HLA-A*2402限制性WT1特异性细胞毒性T细胞(CTL)之TCR基因,经构建逆转录病毒载体后转导WT1-TCR基因至正常外周CD8+T细胞;所获得的CD8+T细胞对靶细胞的杀伤效应经标准51Cr释放试验测定。结果 WT1-TCR基因转导后的正常外周CD8+T细胞显示出对WT1多肽负载的HLAA*2402+LCL细胞的特异性杀伤作用,同时TCR基因改造后的CD8+T细胞可特异性杀伤HLA-A*2402及WT1表达阳性的肺癌细胞株而不对HLA-A*2402表达阳性的正常细胞产生杀伤作用。结论这些数据论证了WT1-TCR基因转导正常外周T细胞具有与亲代CTL一致的特异性杀伤特性,提示该方法用于过继性细胞免疫疗法治疗肺癌具有可行性。Objective To investigate the cytotoxicity of normal CD8＋ T lymphocytes retrovirally transduced with WT1 peptide-specific T-cell receptor （TCR） genes against human lung cancer cells. Methods HLA-A＊2402-restricted and WT1 peptide-specific TCR-α/β genes were cloned from a cytotoxic T lymphocyte clone and inserted into a retroviral TCR expression vector. The cytotoxicity of normal peripheral CD8＋ T cells transduced with the WT1-TCR genes against human lung cancer cells was evaluated using a standard 51Cr release assay. Results The WT1-TCR gene-modified T cells recognized the peptide-pulsed target cells but not the non-pulsed cells. TCR-redirected CD8＋ T cells lysed WTl-overexpressing human lung cancer cells in an HLA-A＊2402-restricted manner, but did not kill normal cells positively expressing HLA-A＊2402. Conclusion These data demonstrate the feasibility of adoptive immunotherapy with TCR-redirected T cell for the treatment of lung cancer.

关 键 词：细胞免疫治疗 T细胞受体 基因转导 细胞毒性T细胞 肺癌 

分 类 号：R734.2[医药卫生—肿瘤]