An Jun, Cai Song-Wang, Li Yun, Zhang Junhang
Division of Cardiothoracic Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China. E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2014 Aug;34(9):1319-23.
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.
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.
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-A2402-restricted manner, but did not kill normal cells positively expressing HLA-A2402.
These data demonstrate the feasibility of adoptive immunotherapy with TCR-redirected T cell for the treatment of lung cancer.
研究经野生型1（WT1）肽特异性T细胞受体（TCR）基因逆转录病毒转导的正常CD8⁺T淋巴细胞对人肺癌细胞的细胞毒性。
从细胞毒性T淋巴细胞克隆中克隆出HLA-A*2402限制性和WT1肽特异性TCR-α/β基因，并插入逆转录病毒TCR表达载体。使用标准的⁵¹Cr释放试验评估经WT1-TCR基因转导的正常外周血CD8⁺T细胞对人肺癌细胞的细胞毒性。
WT1-TCR基因修饰的T细胞识别肽脉冲靶细胞，但不识别未脉冲的细胞。TCR重定向的CD8⁺T细胞以HLA-A2402限制性方式裂解WT1过表达的人肺癌细胞，但不杀伤阳性表达HLA-A2402的正常细胞。
这些数据证明了采用TCR重定向T细胞进行过继性免疫治疗肺癌的可行性。
