基于survivin的“模拟病毒”瘤苗对结肠癌免疫治疗的作用

Immunotherapy effect of mimovirus tumor vaccine based on survivin to colon carcinoma

背景与目的:结肠癌的免疫治疗在肿瘤的综合治疗中发挥了重要作用。本研究以结肠癌的survivin为靶分子,构建基于survivin的"模拟病毒"瘤苗,并探讨该瘤苗对结肠癌的免疫治疗作用。方法:制备基于survivin的"模拟病毒"瘤苗,用扫描电镜和免疫印迹(Western blot)进行鉴定。酶联免疫斑点试验(Enzyme linked immunos-pot assay,ELISPOT)和标准51Cr释放试验分别检测瘤苗所诱导的特异性CTL活性,并对Babl/c小鼠荷瘤模型进行免疫学效应评价。结果:扫描电镜和免疫印迹证实"模拟病毒"瘤苗制备成功,并能有效介导"模拟病毒"瘤苗所携带基因的表达。ELISPOT和标准51Cr释放试验显示体内有效激发抗原特异性CTL效应,可诱导CTL产生IFN-γ等细胞因子,对结肠癌细胞系CT26有明显的杀伤毒性,杀伤率为56.4%;肿瘤治疗实验证实"模拟病毒"瘤苗能有效抑制肿瘤的生长速度,提高荷瘤动物的生存率,与对照组相比差异显著(P<0.05)。结论:基于survivin的"模拟病毒"瘤苗能有效激发出特异性CTL应答,并在荷瘤动物模型中有效抑制结肠癌细胞CT26的生长,提高荷瘤动物的生存率,为新型结肠癌治疗性疫苗的设计提供了新思路。

Background and purpose： Immunotherapy has played an important role in the treatment of colon carcinoma. This study was designed to investigate the immunotherapy of mimovirus tumor vaccine based on survivin that was highly expressed in the colon carcinoma. Methods： Mimovirus tumor vaccine was prepared that was identified by electron microscope and Western blot. ELISPOT and ^51 Cr release assay were used to detect the cytotoxic activity of CTL stimulated by mimovirus tumor vaccine. Babl/c mice models were used to evaluate the mimovirus tumor vaccine effect. Results： The vaccine was prepared successfully that could effectively mediate expression of the genes carried by vaccine particles and be presented by APC cells. The tumor vaccine could induce specific CTL that showed specific cytotoxic effect to colon carcinoma cells CT26 with lysis of 56.4 % and secrete IFN-γ product. In vivo experiment proved that mimovirus tumor vaccine could not only inhibit the tumor growth but also improved survival of animals （P 〈0.05）. Conclusions： Mimovirus tumor vaccine based on survivin can generate specific CTL response that can not only inhibit the tumor growth but also improve survival of animals This result may perhaps provide a new therapeutic vaccine strategy to the patients with colon carcinoma.