基于红细胞膜的抗原递送仿生载体及其在肿瘤免疫治疗中的应用探索

Recently, biomaterials-based non-viral cancer vaccine has became another hot topic in the field of cancer immunotherapy. It is important for the reasonable design of safe and effective cancer vaccine carrier, which effectively reaches antigen presenting cells (APCs) and delivery of cancer vaccine. Spleen is a critical secondary lymphoid organ. Activation of the splenic APCs can stimulate the antitumor immune response. However, there have been few reports of targeted delivery of tumor vaccine to splenic APCs by intravenously administration. Red blood cells (RBCs) or RBC membrane based biomaterials represent a promising cell platform for drug delivery due to their inherent biocompatibility. In this proposal, we will develop an antigen delivery system based on the nanoerythrosomes derived from RBCs inspired by the splenic APC targeting capacity of RBCs. We will systematically explore the capacity of nanoerythrosome based cancer vaccine for targeting delivery and activation of immune system. In addition, we will study this tumor antigen-loaded nanoerythrosomes elicit antigen responses in vivo. We will also generate the “personalized tumor vaccine” obtained by fusing RBCs and surgically removed tumors and in combination with the immune checkpoint blockade to reduce tumor recurrence and metastasis after surgery. Our proposed strategy may represent a novel form of cancer treatment.

基于生物材料的非病毒性肿瘤疫苗是近年来肿瘤免疫治疗领域的又一研究热点。合理设计安全有效的肿瘤疫苗，构建高效靶向抗原呈递细胞的肿瘤疫苗递送系统有重要的科研和临床意义。脾是人类成体最大的淋巴器官，激活脾脏区域的抗原呈递细胞能够激发全身的抗肿瘤免疫反应，产生良好的抗肿瘤效果。然而，通过静脉给药且具有高效靶向脾脏区域功能的肿瘤疫苗目前还鲜有报道。红细胞和基于红细胞膜的生物材料由于其固有的生物相容性，是一类理想的药物递送载体。本项目拟针对肿瘤疫苗领域存在的关键科学问题，巧妙利用红细胞本身性质，构建一种基于红细胞膜的新型肿瘤纳米疫苗，靶向递送肿瘤疫苗至脾脏等免疫器官。本项目将评价基于红细胞膜的肿瘤疫苗预防和治疗黑色素肿瘤的能力，并通过来源于术后切除的肿瘤，构建个性化肿瘤疫苗联合免疫检查点阻断疗法抑制术后癌细胞扩散和复发的潜力。本项目将为开发安全有效的肿瘤疫苗及其免疫联合治疗策略提供新思路。

基于生物材料的非病毒性肿瘤疫苗是近年来肿瘤免疫治疗领域的又一研究热点。合理设计安全有效的肿瘤疫苗，构建高效靶向抗原呈递细胞的肿瘤疫苗递送系统有重要的科研和临床意义。红细胞和基于红细胞膜的生物材料由于其固有的生物相容性，是一类理想的药物递送载体。本项目巧妙利用红细胞本身性质，构建了多种基于红细胞的新型肿瘤疫苗，靶向递送肿瘤疫苗至抗原呈递细胞。本项目评价了基于红细胞的肿瘤疫苗预防和治疗黑色素肿瘤的能力，并通过来源于术后切除的肿瘤，构建个性化肿瘤疫苗联合免疫检查点阻断疗法抑制术后癌细胞扩散和复发的潜力。本项目为开发安全有效的肿瘤疫苗及其免疫联合治疗策略提供新思路。