Immunization with synthetic mRNA encoding tumor-associated antigens is an emerging vaccine strategy for the treatment of cancer. In order to prevent mRNA degradation, promote antigen-presenting cells antigen presentation, and induce an anti-tumor immune response, we investigated the nasal administration of mRNA vaccines with positively charged protamine to concentrate mRNA, form a stable polycation-mRNA complex, and encapsulate the complex with DOTAP/Chol/DSPE-PEG cationic liposomes. Cationic liposome/protamine complex (LPC) showed significantly greater efficiency in uptake of vaccine particles in vitro and stronger capacities to stimulate dendritic cell maturation, which further induced a potent anti-tumor immune response. Intranasal immunization of mice with cationic LPC containing mRNA encoding cytokeratin 19 provoked a strong cellular immune response and slowed tumor growth in an aggressive Lewis lung cancer model. The results of this study provide evidence that cationic LPC can be used as a safe and effective adjuvant and this mRNA formulation provides a basis for anti-cancer vaccination of humans.

用编码肿瘤相关抗原的合成mRNA进行免疫是一种新兴的治疗癌症的疫苗策略。为了防止mRNA降解，促进抗原呈递细胞抗原呈递并诱导抗肿瘤免疫反应，我们研究了鼻腔给药带有正电荷鱼精蛋白的mRNA疫苗以浓缩mRNA，形成稳定的聚阳离子-mRNA复合物并包囊的方法。与DOTAP / Chol / DSPE-PEG阳离子脂质体形成复合物。阳离子脂质体/鱼精蛋白复合物（LPC）在体外摄取疫苗颗粒方面显示出明显更高的效率刺激树突状细胞成熟的能力更强，从而进一步诱导了有效的抗肿瘤免疫反应。在含有攻击性Lewis肺癌模型的阳离子LPC包含编码细胞角蛋白19的mRNA的阳离子LPC的小鼠进行鼻内免疫，可引起强烈的细胞免疫反应并减慢肿瘤的生长。这项研究的结果提供了证据，表明阳离子LPC可以用作安全有效的佐剂，并且该mRNA制剂为人类抗癌疫苗接种提供了基础。