Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, No.1160 Shengli South Street, Yinchuan 750004, PR China.
Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, No.1160 Shengli South Street, Yinchuan 750004, PR China.
Cell Immunol. 2020 Aug;354:104143. doi: 10.1016/j.cellimm.2020.104143. Epub 2020 Jun 4.
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 进行免疫接种是一种新兴的癌症治疗疫苗策略。为了防止 mRNA 降解、促进抗原呈递细胞呈递抗原，并诱导抗肿瘤免疫反应，我们研究了用带正电荷鱼精蛋白的 mRNA 疫苗进行鼻腔给药，以浓缩 mRNA，形成稳定的多阳离子-mRNA 复合物，并将复合物用 DOTAP/Chol/DSPE-PEG 阳离子脂质体包裹。阳离子脂质体/鱼精蛋白复合物（LPC）在体外摄取疫苗颗粒的效率显著更高，并且具有更强的刺激树突状细胞成熟的能力，这进一步诱导了强烈的抗肿瘤免疫反应。用含有编码细胞角蛋白 19 的 mRNA 的阳离子 LPC 对小鼠进行鼻腔免疫接种，引发了强烈的细胞免疫反应，并在侵袭性 Lewis 肺癌模型中减缓了肿瘤生长。这项研究的结果提供了证据，证明阳离子 LPC 可用作安全有效的佐剂，并且这种 mRNA 制剂为人类的抗癌疫苗接种提供了基础。
