肿瘤免疫治疗近来取得的突破性进展，让人们看到了肿瘤治愈的希望。与传统疗法相比，肿瘤疫苗借助机体自身的免疫功能消除肿瘤细胞，具有不良反应小、特异性高、作用范围广等特点。但目前肿瘤疫苗的临床表现尚需提高。本课题全面分析了肿瘤疫苗在载体设计中的不足，认为特异性靶向树突状细胞（DC）是提高肿瘤疫苗安全性和有效性的重要手段。前期试验中，我们意外发现将氢氧化铝制成纳米粒后，具有极高的DC细胞亲和性，几乎不被其他正常细胞或肿瘤细胞摄取，本课题中我们拟对其分子机制进行阐释。此外，鉴于机体的免疫耐受和免疫抑制促进了肿瘤的生长转移，我们提出在肿瘤疫苗的设计中应将促进应答与消除抑制的手段相结合，双向促进免疫应答的产生。我们设计用氢氧化铝纳米粒包载肿瘤抗原肽，Toll样受体激动剂和沉默共抑制分子的小干扰RNA。该肿瘤疫苗载体的构建，将为传统铝盐佐剂的临床应用开拓新的方向，为安全高效的肿瘤疫苗的设计提供新的思路。

Breakthroughs in tumor immunotherapy light up the hope for cancer treatment. In comparison with traditional therapies, anti-tumor vaccination is a safe strategy with high specificity by eliminating tumor cells with the help of the immune system. Nevertheless, the clinical effects of anti-tumor vaccination still need improvement. In this project, we will provide a comprehensive analysis of the deficiencies in current design of tumor vaccines, and put forward the concept that dendritic cells (DCs) targeting is the key to improve the safety and efficacy of tumor vaccines. In the preliminary studies, we have accidentally found that nanoparticles formulated with aluminum hydroxide exhibited extremely high affinity with DCs, and were barely taken-up by normal cells or tumor cells. Here we will clarify the molecular mechanisms of this phenomenon. Since the immune tolerance and immune suppression promote tumor growth and metastasis, we will combine the strategies of stimulating immune response and removing immune suppression to strengthen the effectiveness of tumor vaccines. In the current project, tumor antigen peptides, Toll-like receptor agonist and small interfering RNA (siRNA) which silences immune inhibitory molecules are co-encapsulated in the aluminum hydroxide nanoparticles. The construction of this cancer vaccine delivery system will broaden the application of aluminum-based adjuvants and provide a new design strategy for safe and effective cancer vaccines.