胃肠道肿瘤相关抗原表位嵌合病毒样颗粒疫苗构建及其免疫原性研究

项目名称： 胃肠道肿瘤相关抗原表位嵌合病毒样颗粒疫苗构建及其免疫原性研究

项目编号： No.31470891

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 沈贤

作者单位： 温州医科大学

项目金额： 80万元

中文摘要： 胃肠道肿瘤是我国的多发病，居恶性肿瘤首位，疫苗则是其防治的根本途径。以抗原表位为基础的分子疫苗已显示了其防治肿瘤的良好前景，但表位疫苗的免疫原性弱和其天然构象问题仍急待解决。鉴于人乳头瘤病毒（HPV）结构蛋白可在体外真核表达系统自组装形成病毒样颗粒（VLPs），利用其携带异源表位疫苗，具有免疫原性强且保持其异源表位空间构象不变等优点。本研究拟选择胃肠肿瘤组织中高表达的肿瘤抗原MAGE-3、HER-2/neu和CEA，通过对其CTL和B细胞表位的预测、筛选和鉴定，并将胃肠肿瘤相关抗原表位基因插入HPV16 L1 蛋白的羧基端，制备以HPV16 L1为载体含MAGE-3/ HER-2/neu/CEA多表位的嵌合VLPs，并进一步探讨其刺激机体产生的免疫保护效应。目的是使嵌合VLPs能刺激机体免疫系统同时产生肿瘤抗原特异性的抗体反应和CTL 反应，从而达到用特异性免疫方法防治胃肠肿瘤。

中文关键词： 胃肠道肿瘤；肿瘤相关抗原；表位；病毒样颗粒；疫苗

英文摘要： Gastrointestinal cancer is a common disease and ranked first in all kinds of malignant tumors in our country. Nowadays, the vaccine is considered as the fundamental way to cancer prophylaxis and prevention,and molecular vaccine which based on epitopes has shown its good application.However, the disadvantages of epitope vaccines on weak immunogenicity and natural conformation need to further study.The L1 structural protein of the human papillomavirus(HPV) expressed in eukaryotic expression system in vitro can self-assemble into virus-like particles(VLPs) and be used to carry heterologous epitopes with strong immunogenicity and stable epitope conformation.In this study MAGE-3, HER-2/neu and CEA tumor antigen which highly expressed in various gastrointestinal cancer will be selected as the targets of potential vaccine. After prediction,screening and identification of their CTL and B cell epitopes,the sequence containing these epitopes will be inserted into the carboxyl terminus of HPV16 L1 protein to produce chimeric VLPs. The immune responses and protective effects of the chimeric VLPs contained MAGE-3 / HER-2/neu/CEA multi-epitopes will further be evaluated. The aim of this study is to generate specific antibodies and CTL reaction after immunized by chimeric VLPs and to prevent gastrointestinal tumor.

英文关键词： gastrointestinal tumor;tumor-related antigen;epitope;virus like particle;vaccine