携带白细胞介素12基因逆转录病毒载体包装细胞株体内直接注？…

目的 研究体内直接注身携带白细胞介素１２（ｍＩＬ－１２）逆转录病毒载体包装细胞株对体内肝癌细胞生长抑制作用，探索基因治疗新途径。方法 构建携带ｍＩＬ－１２的逆转录病毒载体，将载体转染包装细胞株，用该细胞株分别在大鼠腹腔内与肝癌细胞株混合接种，在肝癌局部及脾内直接注射，观察对肝癌生长抑制作用及其对大鼠毒性反应、免设功能变化。结果 应用该细胞株与肝癌细胞株在腹腔进行混合接种，１：１０以下治疗组可使大鼠

Experimental study of the anti-tumor effects of directly administered packaging cell line of retroviral vector carrying IL-12 gene on hepatoma]

OBJECTIVE: To study the inhibitory effects of vivo directly administered packaging cell line of retroviral vector carrying mouse interleukin-12(mIL-12) on the growth of the vivo established hepatoma and to explore a new way for hepatoma gene therapy. METHODS: Retroviral vector carrying mIL-12 gene was constructed. The vector was transfected to retroviral packaging cell line. Then the cell was injected intra-peritoneally and locally into hepatoma tissues or intrasplenally to observe its effects on the growth of hepatoma and the changes of immunological function in rats. Its toxic effects were also documented. RESULTS: In treatment group, the rats survived permanently with the ratio of the packaging cell to hepatoma cell being less than 1:10, while the survival time of rats was only prolonged when the ratio was more than 1:10. In groups treated locally in the hepatoma tissue or intrasplenally, the rats survived permanantly with the packaging cell line given on the first or the third day, while the rats survived only longer with the packaging cell line given on the fifth or the seventh day. The immunological study showed that the number of hepatoma infiltrating lymphocytes, mainly composed of NK cell and cytotoxic T cell, was increased in the treatment group. The pathological study showed thicking of the vascular wall and sternosis of vascular cavity in hepatoma tissue in the treatment group. CONCLUSION: The directly injected packaging cell line in vivo carrying mIL-12 gene via retroviral vector inhibits the growth of hepatoma. The therapeutical effects of early administration are superior to later one. Direct injection via spleen is a new, safe and effective way for hepatoma therapy with.