基于IRF3/IFN通路探讨香菇多糖联合IRF3腺病毒载体的抗乳腺癌作用及机制研究

项目名称： 基于IRF3/IFN通路探讨香菇多糖联合IRF3腺病毒载体的抗乳腺癌作用及机制研究

项目编号： No.81503392

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张晶

作者单位： 天津中医药大学

项目金额： 18万元

中文摘要： 肿瘤免疫治疗的“减毒增效”作用使其成为未来抗肿瘤治疗的重要方向。但目前单一免疫佐剂通常难以打破机体免疫耐受状态，联合治疗才是未来发展方向。基于香菇多糖和IRF3的重要免疫调节作用，我们利用表达组成型活化IRF3的腺病毒载体（AdIRF3）肿瘤内注射联合香菇多糖腹腔注射，观察其对TUBO乳腺癌肿瘤生长的影响并探索潜在机制。首先确立联合治疗在体外对TUBO生长的影响；再在免疫正常小鼠观察联合治疗对肿瘤生长、循环和肿瘤局部免疫反应的影响；利用Balb/c-nu裸鼠观察适应性免疫应答在联合治疗控制肿瘤生长中的作用；为探索联合治疗增强抗肿瘤免疫的潜在分子机制，利用IFNAR1封闭抗体阻断I型干扰素作用后观察联合治疗的抗肿瘤作用、循环和肿瘤局部免疫反应变化。旨在阐明香菇多糖联合AdIRF3是否存在协同作用及潜在的作用机制，为香菇多糖联合分子免疫佐剂治疗肿瘤提供理论基础。

中文关键词： 乳腺癌；香菇多糖；肿瘤免疫；干扰素调节因子3；I型干扰素

英文摘要： Cancer immunotherapy is one critical filed of anti-tumor therapy based on its low toxicity and high efficiency. However, single adjuvant is hard to overcome the immune suppression induced by tumor. Combined therapy will be the mainstream in the future. Given the pivotal role of lentinan and IRF3 in immune regulation, combined therapy of adenovirus vector expressing constitutively activated IRF3, AdIRF3 (I.T injection), and lentinan (I.P injection) will be tested in TUBO cells bearing mice for the efficiency in controlling tumor growth. Firstly, the combined therapy will be used to treat TUBO in vitro to make sure its direct effect on cells. Secondly, TUBO cells bearing Balb/c mice will be treated and tumor growth as well as corresponding immune responses in peripheral blood and tumor site will be monitored. Moreover, TUBO cells bearing Balb/c-nu mice are used to demonstrate the role of adaptive immune response in controlling the tumor growth of combined therapy. In order to discover the underlying mechanism of combined therapy in activating the antitumor immune response, anti-IFNAR1 antibody will be administrated to establish the role of type I interferon in activating immune response. The aim of our study is to discover whether the lentinan and AdIRF3 have synergic effect in controlling tumor growth and the underlying mechanism, providing a direction for antitumor therapy and the combined therapy of lentinan with molecular adjuvant.

英文关键词： breast cancer;lentinan;tumor immunity;IRF3;type I IFN