新型疫苗FAPt-MT抗肿瘤效应的机制研究

项目名称： 新型疫苗FAPt-MT抗肿瘤效应的机制研究

项目编号： No.81201763

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 衣艳梅

作者单位： 广东医学院

项目金额： 22万元

中文摘要： 作为一种有前景的肿瘤免疫治疗策略，肿瘤多肽疫苗的研究备受重视。然而其实际临床效果却往往不尽人意。究其原因，两个方面的因素不可忽视。一方面是肿瘤自身的因素，即肿瘤细胞基因的不稳定性导致靶抗原变异和丢失引起肿瘤免疫逃逸。因此，肿瘤疫苗的选择从传统的肿瘤细胞表面抗原逐渐转向肿瘤间质细胞表面抗原。表达于肿瘤间质成纤维细胞表面蛋白-成纤维细胞激活蛋白a（FAPa），作为一种极具潜力的抗肿瘤靶标分子正备受关注。另一方面是宿主的因素，荷瘤宿主内抑制性分子的产生，导致机体抗肿瘤功能低下。吲哚胺2，3双加氧酶（IDO）被认为是介导肿瘤免疫耐受的关键环节。因此，我们在前期研究中将IDO特异性抑制剂1-MT修饰至FAPa,构建了嵌合蛋白FAPt-MT，并证实该疫苗具有良好抗肿瘤作用。本课题我们将进一步探讨FAPt-MT对肿瘤微环境的免疫调节作用，阐明其抗肿瘤机制。本研究将为实现该疫苗的推广应用提供有力依据。

中文关键词： FAPt-MT；FAPa表达调控；胃癌；；

英文摘要： As a promising tumor immunotherapy strategy, polypeptide vaccine has attracted more and more attention. However, the tumor vaccines always appear the worse clinical results in practical application. To investigate its reason, there are existing two factors. On the one hand is the reason of tumor itself. Targeted tumor antigens variation and lost resulted from genomic instability led to tumor immune escape. Therefore, the choice for tumor vaccine is turning from antigens of tumor cell to antigens of tumor stromal cell. Fibroblast activation protein α (FAPα) derived from tumor associated fibroblasts is frequently explored as a candidate target for tumor therapy. On the other hand is the host reason. Inhibitory molecules generated in the host resulted in its low antitumor function. Indolamine2,3-dioxygenase (IDO) is supposed to play important roles in mediating tumor immune tolerance. As above, we constructed the new tumor vaccine FAPt-MT and confirmed its anti-tumor activity in our previous study. In this study, we will further explore anti-tumor mechanisms of the new tumor vaccine and how FAPt-MT regulate the tumor immune microenvironment. This study will provide the first hand information for its application and dissemination.

英文关键词： FAPt-MT；mechanism of FAPa expression；gastric carcinoma；；