转4-1BBL基因细胞诱导带瘤宿主抗瘤效应的体内研究  

Antitumor immunity elicited by 4-lBBL gene transfected Hepal-6 in vivo

作　　者：李晓虹[1] 李晓冬[2] 卫立辛[2] 陈列平[2] 郭亚军[2] 黄建勇 吴孟超[4] 

机构地区：[1]上海出入境检验检疫局动植物与食品检验中心,200135 [2]上海第二军医大学国际合作肿瘤研究所 [3]上海华源生命科学研究开发有限公司 [4]上海第二军医大学东方肝胆外科医院

出　　处：《中华肝脏病杂志》2002年第6期409-412,共4页Chinese Journal of Hepatology

基　　金：国家自然科学基金(39928012;39730440);上海市博士后基金(沪科2000第478号)

摘　　要：目的 观察协同刺激分子4-1BB Ligand(4-1BBL)基因导入小鼠肝癌细胞Hrpal-6后在小鼠体内诱导的抗瘤效应。方法 应用逆转录病毒载体,将小鼠4-1BBL导入小鼠肝癌细胞Hepal-6细胞中,Histidinol(HisD)筛选后获高表达4-1BBL分子附性细胞克隆,经丝裂霉素C(MMC)处理制备成肿瘤细胞瘤苗TCV4-1BBL,观察其对下同动物模型的体内免疫保护作用和免疫治疗作用。结果(1)能对同系肝癌细胞产生完全的免疫保护作用,并能保持无瘤状志长期存活(100d以上)。(2)对早期(接种 7d)形成的肿瘤有强的治疗作用。(3)对晚期(接种14d)肿瘤,有明显的治疗作用,使大部分小鼠的肿瘤消退。结论4-1BBL修饰的肿瘤细胞疫苗能明显刺激增强带瘤宿主的抗瘤效应。Objective To study the effects of 4-1BBL on antitumor immunity induced in vivo by murine 4-1BBL gene transfected Hepal-6. Methods Retrovirus vector was used to transfer the 4-1BBL gene into syngeneic murine heptocellular carcinoma cell line Hepal-6. The products were termed as Hepal-6/4-lBBL, and then the TCV4-1BBL was obtained by treating them with mitomycin (MMC). Three models (immunological model, early model, and later model) were established to study the antitumor effects of TCV4-1BBL. Results (I )In immunological models, the syngeneic mice were completely protected by inoculation with TCV4-1BBL, survived free from tumor for a long period (over 100 days). (2)In early models (7 days after inoculation), Hepal-6 tumor cells showed strong immunogenicity effects and (3) In later models (14 days after inoculation), they had obvious antitumor effects and most of the tumors were disappeared. Conclusions The antitumor effect against syngeneic murine hepatocellular carcinoma in vivo is obviously enhanced by treating them with TCV4-1 BBL.

关 键 词：4-1BBL 肝细胞癌 肿瘤疫苗 基因疗法 小鼠 转基因 

分 类 号：R730.3[医药卫生—肿瘤] R735.[医药卫生—临床医学]