肿瘤坏死因子α基因转导人脑胶质瘤浸润淋巴细胞的抗肿瘤活性研究

The Antitumor Activity of Human Glioma Infiltrating Lymphocytes Transduced by TNF α Gene

应用脂质体转染技术构建能表达肿瘤坏死因子－α（ＴＮＦ－α）基因的重组逆转录病毒。采用鱼精蛋白促进法，将重组病毒介导ＴＮＦ－α基因转染人脑胶质瘤浸润淋巴细胞（ＧＩＬ）。在体外，转染后的ＧＩＬ（ＴＮＦ－α／ＧＩＬ）的抗肿瘤活性比ＧＩＬ＋ＩＬ－２强２～５倍。在荷瘤裸鼠体内，ＴＮＦ－α／ＧＩＬ能显著抑制肿瘤生长。因此。

In order to study the antitumor activity of human glioma infiltrating lymphocytes (GIL) transduced by TNF α gene, retroviral vector PLTSN with Neo r gene driven by SV 40 early promoter, TNF α gene driven by LTR and packaging cell line PA 317 were used to clone cell line LTSN/PA317 producing LTSN at high titer. The recombinant glioma, to have a king of GIL (TNF/GIL) for production of TNF α at certain level. Inject TNF α/GIL into the body for nude mice through abdominal cavity or in the site of the tumor respectively. In vitro, before later transduction, the growth and expression of GILs surface markers showed no significant difference from TNF α/GIL, while the transduced GIL/(tnf/GIL) grows successfully in high concentration of G 418, suggesting TNF α/GIL contain Neo r cDNA; TNF α/GIL has two to five folds of cytotoxicity to SHG 44 or autoglioma cells compared with GIL+IL 2; TNF α/GIL have various inhibitory efficiencies to the growth of tumor in nude mice. Human glioma infiltrating lymphocytes transduced by TNF α gene may be a useful antitumor effector to human glioma.