IL-23基因修饰的树突细胞疫苗联合β-榄香烯对小鼠胰腺癌生长的影响  

Immunotherapeutic Effects of β-elemene Combined with Interleukin-23 Gene-modified Dendritic Cells on Murine Pancreatic Carcinoma

作　　者：谭广[1] 王忠裕[1] 王晓刚 程雷[1] 殷朔[1] 

机构地区：[1]大连医科大学附属一院普外二科,辽宁大连116011 [2]陕西省蒲城县人民医院普外科,陕西蒲城715500

出　　处：《癌症》2006年第9期1082-1086,共5页Chinese Journal of Cancer

基　　金：辽宁省科技厅自然基金资助项目(No.20042138)~~

摘　　要：背景与目的:树突细胞(dendriticcells,DC)疫苗是目前最具应用潜能的治疗性疫苗,功能性细胞因子能显著增强DC的活性及其诱导的宿主抗肿瘤作用,利用细胞因子基因修饰DC是当今肿瘤免疫治疗中最活跃的领域。本研究探讨β-榄香烯联合白细胞介素-23(interleukin-23,IL-23)修饰的DC疫苗对胰腺癌小鼠的协同抗肿瘤作用。方法:克隆并构建IL-23基因真核双表达载体,转染DC并负载肿瘤抗原后制备成疫苗。将IL-23基因转染的DC疫苗、空质粒转染的DC疫苗、未转染的DC疫苗及对照生理盐水分别注射小鼠,体外观察各组小鼠脾脏T淋巴细胞IFN-γ及IL-4的分泌。体内观察β-榄香烯联合DC疫苗对荷胰腺癌小鼠肿瘤生长的抑制作用及对小鼠存活期的影响。结果:基因测序证实IL-23基因克隆及双表达载体构建成功,转染后DC共刺激分子MHC-Ⅰ和MHC-Ⅱ的表达增强。接种IL-23转染DC疫苗后小鼠的免疫防御能力显著增强,有效地延缓并防御接种肿瘤的发生。DC介导的免疫应答促进了IFN-γ生成型Th1细胞的产生,未转染DC疫苗组和空质粒转染DC疫苗组IL-4分泌量与IL-23转染的DC疫苗组比较差异有显著性(P<0.05);IL-23转染DC疫苗组IFN-γ的分泌与其他各组比较差异有显著性(P<0.01)。β-榄香烯联合IL-23转染DC疫苗组肿瘤生长受到显著抑制,该组小鼠存活期与DC组、NS对照组及β-榄香烯组比较差异有极显著性(P<0.01)。结论:IL-23修饰DC疫苗可强化宿主针对特异肿瘤的Th1及CTL的免疫应答,使宿主不仅产生防御性免疫反应而且增强自动免疫能力。β-榄香烯有一定的协同抗癌作用。BACKGROUND ＆ OBJECTIVE： Dendritic cell（DC） vaccine is a kind of treatment vaccine with clinical application potency. Functional cytokines can enhance anti-tumor immune response of dendritic cells. This study was to investigate the protective effects on murine pancreatic carcinoma by β-elemene combined with bone marrow-derived dendritic cells （BM-DCs） modified with murine interleukin （IL）-23 gene. METHODS： The murine IL-23 cDNA was sub-cloned into dual-expression vector. DCs were pulsed with tumor cell lysate after modified by IL-23 gene. Mice were injected with IL-23-transfected DC vaccine, non-transfected DC vaccine, and sodium, respectively. The immune preventative and immunotherapeutic effects of DC vaccines on mice and the cytokine release in vivo were assessed. Effects of vaccine combined with 13-elemene on tumor growth and survival period of the mice were observed. RESULTS： IL-23 protein apparently increased the antigen-presenting ability of DCs. After the vaccination of DC vaccines, IFN-γ production in treatment group was significantly more than that of the control group （P〈0.01）, as well as, IL-4 production was less than that in the normal group （P〈0.05）. Tumor growth was obviously inhibited and the survival period of the mice was obviously prolonged in β-elemene combined with DC vaccine group than in DC, β- elemene, or control group （P〈0.01）. CONCLUSIONS, IL-23-modified DC vaccines can enhance specific Thl-type and CTL response against pancreatic carcinoma cells, induce not only preventative immunity, but also auto-immunity against pancreatic carcinoma. Moreover, β-elemene has great collaborative anti-tumor function.

关 键 词：IL-23基因 树突细胞 胰腺肿瘤 免疫反应 Β-榄香烯 

分 类 号：R735.9[医药卫生—肿瘤]