中文摘要：

目的构建小鼠甲胎蛋白（mAFP）基因转染的树突状细胞（DC）瘤苗，评价其在C57BL／6J小鼠自然肝癌诱发过程中的免疫保护作用。方法诱导、扩增DC。将表达mAFP的重组腺病毒颗粒转染DC，检测转染前后DC细胞表面分子MHCI、MHCII、CD18a（LFA）、CD54（ICAM）、CD80（B7．1）和CD86（B7．2）等的变化。80只C57BL／6J雄性小鼠随机分为单纯接种DC组、接种转mAFP基因DC（pAdBM5-mAFP-DC）组、单纯接种重组质粒（pAdBM5-mAFP）组和正常对照组，每组20只。实验组在每只小鼠的左肋部注射5×10^5个细胞，连续免疫3d，以后每7d接种疫苗1次，继续免疫4次；正常对照组仅注射0．1ml PBS。在接种免疫的同时，给以二乙基亚硝胺（DEN）、四氯化碳（CCl4）和乙醇联合诱癌。诱癌20周后处死小鼠，检查成瘤情况，并对肝脏标本进行组织病理学检查。结果成功构建了转基因pAdBM5-mAFP-DC瘤苗；mAFP基因转染后的DC表面高表达MHCⅠ、MHCⅡ、CD18a、CD54、CD80和CD86等共刺激分子，其分子表达率分别为69．3％、41．0％、42．1％、63．2％、39．4％和38．6％，与转染前差异有统计学意义（P〈0．05）。单纯接种DC组、pAdBU5-mAFP-DC组、pAdBM5-mAFP组和正常对照组的肝癌发生率分别为65．0％、25．0％、70．0％和75．0％，pAdBM5．mAFP．DC组与其他组比较，差异有统计学意义（P〈0．05）。结论pAdBM5-mAFP-DC瘤苗免疫自然诱癌的C57BL／6J小鼠，可降低肝癌的发生率，对肝癌的发生有免疫保护作用。

英文摘要：

Objective To construct a dendritic cell vaccine transduced by murine alpha-fetoprotein （mAFP） gene, and evaluate its immunoproteetive effect on C57BL/6J mice during the induction of hepatocellular carcinoma by diethylnitrosamines, carbon tetraehloride and ethanol. Methods Dendritic cells （DCs） were induced and augmented by routine IL-4 and GM-CSF, and transfeeted by recombinant adenovirus engineered with mAFP gene. Major MHC class Ⅰ and Ⅱ , B7.1 （CD80） , B7.2 （ CD86 ）, CD18a, and CD54 molecules on DC were analyzed by FACS. 80 C57BL/6J male mice were randomly divided into 4 groups （20 mice per group） ： Simple DC inoculated group, pAdBMS-mAFP-DC inoculated group, pAdBMS-mAFP plasmid inoculated group, and PBS control group. They were immunized once with 5 × 105 DCs （0.1 ml）/mouse administered s.e. in the left flank or 100 mg pAdBMS-mAFP plasmid/mouse administered i.m. in the left tibialis anterior muscle. Inoculation was conducted once a week for 4 weeks after 3 times consecutive immunization initially. At the same time of immunization, DEN/CCl4/ethanol were given to induce hepatocellular carcinoma. Tumor incidence was assessed after 20 weeks. Results A transgenie DC vaccine was successfully constructed and the mAFP transgenie DCs expressed high level molecules of major MHC class Ⅰ and Ⅱ , B7.1, B7.2, CD18a, and CD54. After the 20-week induction, the incidence of primary hepatocellular carcinoma （ PLC ） was 70.0% in simple DC inoculated group, 25.0% in pAdBMS-mAFP-DC inoculated group, 65.0% in pAdBMS-mAFP plasmid inoculated group, and 75.0% in PBS control group. There was a significant difference between group B and other groups （ P 〈 0.05）. Conclusion mAFP transgenie DC tumor vaccine inoculation may induce strong immunoproteetion against liver carcinogenesis and tumor development and reduce PLC incidence induced by DEN/CCl4/ ethanol.