Guo Jueshuo, Ma Shijie, Mai Yaping, Gao Ting, Song Zhihua, Yang Jianhong
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; Department of Preparation Center, General Hospital of Ningxia Medical University, No. 1160 Shengli South Street, Yinchuan 750004, PR China.
Int Immunopharmacol. 2022 Dec;113(Pt A):109254. doi: 10.1016/j.intimp.2022.109254. Epub 2022 Oct 14.
mRNA vaccination is considered to be a promising strategy for tumor immunotherapy. Among, adequate antigen expression and regulation of tumor immune microenvironment are still the key to achieving therapeutic immounotherapy. In oreder to protect mRNA delivered to cells and reverse damaged dendritic cells(DCs), a novel vaccine delivery system composed of an α-Galactose ceramide/cationic liposome complex(α-GC-Lip) was constructed. The α-GC-liposome/protamine/mRNA vaccine complexes(α-GC-LPR) enabled the mRNA to be successfully translated into protein in the cytoplasm of antigen-presenting cells. Further, α-GC-LPR could stimulate dendritic cell maturation via significantly increasing the expression of bone marrow-derived cells(BMDCs) surface molecules and secretion of cytokines to improve the efficacy of immunotherapy. In vivo study, the α-GC-LPR was combined with programmed cell death protein 1(PD-1) inhibitor could activate natural killer cell(NK), T cells as well as significantly reduce the immunosuppression of immune cells, which induced strong antigen-specific immunity in breast cancer model. Our study indicated that the α-GC-LPR combined with immune checkpoint inhibitors as a potential design strategy to effectively enhance the antitumor immune response.
信使核糖核酸（mRNA）疫苗接种被认为是肿瘤免疫治疗的一种有前景的策略。其中，充足的抗原表达和肿瘤免疫微环境的调节仍是实现治疗性免疫治疗的关键。为了保护递送至细胞的mRNA并逆转受损的树突状细胞（DC），构建了一种由α-半乳糖神经酰胺/阳离子脂质体复合物（α-GC-Lip）组成的新型疫苗递送系统。α-GC-脂质体/鱼精蛋白/mRNA疫苗复合物（α-GC-LPR）使mRNA能够在抗原呈递细胞的细胞质中成功翻译为蛋白质。此外，α-GC-LPR可通过显著增加骨髓来源细胞（BMDC）表面分子的表达和细胞因子的分泌来刺激树突状细胞成熟，从而提高免疫治疗的疗效。在体内研究中，α-GC-LPR与程序性细胞死亡蛋白1（PD-1）抑制剂联合使用可激活自然杀伤细胞（NK）、T细胞，并显著降低免疫细胞的免疫抑制，在乳腺癌模型中诱导强烈的抗原特异性免疫。我们的研究表明，α-GC-LPR与免疫检查点抑制剂联合使用是一种有效增强抗肿瘤免疫反应的潜在设计策略。
