靶向FGFR1新型复方DC疫苗抗肿瘤血管生成研究

项目名称： 靶向FGFR1新型复方DC疫苗抗肿瘤血管生成研究

项目编号： No.81460461

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郑少江

作者单位： 海南医学院

项目金额： 48万元

中文摘要： 细胞穿膜肽CPP44是一类只针对肿瘤细胞具有超强细胞膜穿透能力的短肽，可携带大分子物质进入细胞且对正常细胞无毒副作用。MIP3α是DC特异性趋化因子，能有效提高DC递呈抗原能力。我们前期已证实靶向FGFR1免疫治疗具有显著抗肿瘤效果，且发现重组单纯疱疹病毒1型(HSV1)-MIP3α溶瘤病毒既保留了HSV1溶瘤特性，还携带有MIP3α信息。本项目拟在前期基础上将转染高效表达MIP3α/CPP44基因的病毒重组子与FGFR1适配体(aFR1)用纳米脂质体包裹偶联成aFR1/HSV1-MIP3α-CPP44生物反应器，该生物反应器能让肿瘤部位靶向富集高浓度MIP3α，加上HSV1溶瘤和aFR1靶向抗肿瘤血管生成作用，将可能极大增强它们对肿瘤细胞和/或肿瘤新生血管特异性靶向杀伤作用，并研究该多功效生物反应器是否是一种简单而有效的体内DC疫苗模式。我们将通过体内外实验研究其抗肿瘤作用和机理。

中文关键词： 碱性成纤维细胞生长因子1；型受体；巨噬细胞炎性蛋白3α；细胞穿膜肽；树突状细胞疫苗；靶向治疗

英文摘要： Cell penetrating peptides 44（CPP44 ）is a kind of short peptide with the super membranepenetrability targeting only tumor cells and can carry large molecules into cells without any toxic side effect on normal cells. MIP3α, the most important specific chemokine, can effectively improve the antigens presenting ability of DC. We have previously proved that immunotherapy targeting FGFR1 has obvious anti tumor effect, and found that the oncolytic virus recombinant herpes simplex virus type 1 (HSV1)-MIP3α not only retains the oncolytic properties of HSV1, but also carries the information of MIP3α. On the basis of previous work, We propose here to use the virus recombinant transfected with MIP3α/CPP44, along with FGFR1 aptamer (aFR1) encapsulated by nano liposome and produce a final complex product: aFR1/HSV1-MIP3α-CPP44 bioreactor. This bioreactor will generate high concentrated MIP3α combined with CPP44 at the targeted tumor site, and the aFR1 can also inhibit angiogenesis in tumor.This bioreacctor will greatly enhance specifically targeted killing effect on tumor cells and/or tumor angiogenesis. Accordingly, such aFR1/HSV1-MIP3α-CPP44 bioreacctor is very likely a promising in vivo DC vaccine. We will investigate the mechanism by in vivo and in vitro.

英文关键词： Fibroblast growth factor receptor1(FGFR1);Macrophage inflammatory protein3a(MIP3a);Cell penetrating peptides(CPP);DC vaccine;Targeting therapy