南方医科大学学报

南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (09): 1319-.

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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

安军，蔡松旺，李昀，张军航   

  • 出版日期:2014-09-20 发布日期:2014-09-20

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

  • Online:2014-09-20 Published:2014-09-20

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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
HLA-A*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。

Abstract: 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 WT1-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.