摘要
目的 研究IL-2和B7-1基因联合修饰的肝癌瘤苗预防肝癌形成的作用。方法 用重组腺病毒为载体,将目的基因导入小鼠Hepal-6肝癌细胞株,MMC处理后制成肝癌瘤苗,免疫同系小鼠,观察抗亲代Hepal-A细胞攻击的免疫保护作用,并检测免疫小鼠的细胞免疫功能。共设6个实验组:IL-2和B7-1双基因修饰瘤苗组出(Hep6-IL2/B7),IL-2基因瘤苗组(Hep6-IL2),B7-1基因瘤苗组(Hen6-B7),BGFP基因瘤苗组,野生瘤苗组和培养液对照组。结果 各组瘤苗的免疫保护作用:上述 6组小鼠的中位生存期分别为 68、59、54、51、48、38 d,其中 Hep6-IL2/B7瘤苗组生存期最长,且瘤体积最小(Z值为3.20～44.10,P<0.05)。经细胞免疫功能检测和细胞毒活性实验显示以Hep6-IL2/B7瘤苗免疫后可诱导显著提高的NK、LAK和CTL活性(分别为29.0％±2.5％、65.0％±2,9％和83.1％±1.5％,与其它实验组比P<0.05)。结论 IL-2和 B7-1双基因肝癌瘤苗可诱导小鼠产生活化的针对亲代癌细胞的特异性CTL细胞,具有比单基因及常规瘤苗更强的防癌的作用,有希望成为预防肝癌复发转移的治疗手段。
Objective To study the immunoprotective effect of IL-2 and B7-1 gene co-transfected liver cancer vaccine on hepatocarcinogenesis in mice. Methods The murine liver cancer cell strain Hepal-6 was transfected with IL-2 and/or B7-1 gene via recombinant adenovirus vectors and the liver cancer vaccines were prepared. C57BL/6 mice were immunized with the vaccines and challenged with the parental Hepal-6 cells afterwards. The immunoprotection was investigated and the reactive T cell line was assayed. Results The effect of the Hep6-IL2/B7 vaccine on the onset of tumor formation was the strongest. The media survival time of the mice was the longest (68 days, P<0.05) and the implanted tumor was the smallest (P<0.05). The effect of single IL-2 or B7-1 gene-transfected vaccine was next to the co-transfected gene group with the mean survival time being 59 and 54 days, respectively. The mean survival time of wild or BGFP gene modified vaccine immunized group was 51 and 48 days, respectively. The control group all died within 38 days and the implanted tumor was the largest (P><0.05). The cellular immunofunction test and cytotoxicity study showed that the mice immunized with the Hep6-IL2/B7 vaccine gained significantly increased NK, LAK and CTL activity (29.0% + 2.5%, 65.0% + 2.9%, 83.1 % + 1.5% respectively, compared with other groups P<0.05). Conclusions The IL-2 and B7-1 gene co-transfected liver cancer vaccines can induce the mice to produce activated and specific CTL against the parental tumor cells, and demonstrate stronger effect on the hepatocarcinogenesis than single gene modified or the regular tumor vaccine. Therefore, the vaccines may become a novel potential therapy for recurrence and metastases of HCC.
出处
《中华肝脏病杂志》
CAS
CSCD
2002年第6期417-420,共4页
Chinese Journal of Hepatology
基金
国家九五攻关项目(96-906-01-20)
