肿瘤疫苗是目前免疫治疗的一个热点，疫苗制剂诱导产生强烈的肿瘤特异T细胞反应，有效地促进机体排斥并消灭肿瘤。我们已开发能够激活STING信号通路的、制剂极为简便、且很低毒性的纳米疫苗载体，PC7A；该载体可以与任意肿瘤特异抗原肽结合，以很低的剂量高效诱导机体产生强烈的抗原特异性T细胞反应，并在多个肿瘤模型中显示出明显的抗肿瘤效果。然而，任何单一的治疗方法都难以独自有效清除肿瘤，尤其是大的已经建成的肿瘤。对肿瘤疫苗而言，如何突破已建成的肿瘤屏障、克服肿瘤内部强烈的免疫抑制环境等是当前急需解决的难题。局部放疗能够有效打破肿瘤屏障、增强T细胞反应；同时放疗引起大量DNA断裂和突变，暴露和产生很多肿瘤新抗原，为纳米疫苗带来新靶点。因此，我们拟开展肿瘤疫苗与局部放疗的联合治疗研究，利用局部放疗促进和拓展纳米疫苗的抗肿瘤效果，并深入分析其作用机制，为将来针对肿瘤的临床治疗转化奠定基础。

Cancer vaccine became a powerful approach in cancer immunotherapy recently. Well formulated vaccine could induce strong tumor specific T cell response, which subsequently promote the tumor rejection and clearance. We have developed a minimalist nanovaccine by a simple physical mixture of an antigen with a synthetic polymeric nanoparticle, PC7A NP, which activated STING (Stimulator of Interferon Genes) innate immune signal pathway and generated strong T cell response with low systemic cytokine expression. This nanovaccine produced potent tumor growth inhibition in multiple tumor models. However, nanovaccine alone could not reject big established tumor due to the established tumor barrier and immunosuppressive environment. Increasing evidence has shown that radiation therapy (RT) can break tumor barrier, augment adaptive T cell responses to tumors, thereby decreasing immunosuppression to mediate tumor eradication. At the same time, RT induced DNA damage can produce a lot of neo-antigens for efficient immunotherapy. Here, we hypothesize that combination therapy of nanovaccine with radiation therapy will produce a much better therapeutic effect against big established tumor, which will provide a novel strategy for the cancer treatment.