Zhang Wenli, Guan Jiahao, Wang Wenwen, Chen Guo, Fan Li, Lu Zifan
Translational Medicine Center of Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
Medical Laboratory Center of Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
Genes Immun. 2024 Dec;25(6):514-524. doi: 10.1038/s41435-024-00305-3. Epub 2024 Nov 26.
The development of personalized anticancer vaccines based on neoantigens represents a new direction in cancer immunotherapy. The latest advancement in dendritic cell (DC) tumor vaccine construction involves loading DC with mRNA-encoding neoantigens, which allows for rapid production and is suitable for personalized preparation. Cell-penetrating peptides (CPPs) are emerging as biological delivery systems in which negatively charged nucleic acids can be wound onto the cationic CPP backbone to form nanoscale complexes. This preparation method facilitates standardization. If DC can express and present neoantigen mRNA at high levels, it holds promising application potential. In this study, we developed a neoantigen-mRNA/DC vaccine using candidate neoantigens from mouse colon cancer (MC38) and examined its immune and antitumor effects. The results demonstrated that neoantigen-mRNA/DC vaccines induced strong T cell immune responses and exhibited significant antitumor effects, effectively preventing tumor growth. Our study provides an experimental basis for further optimizing the preparation of DC vaccines and reducing their costs.
基于新抗原的个性化抗癌疫苗的开发代表了癌症免疫治疗的新方向。树突状细胞（DC）肿瘤疫苗构建的最新进展包括用编码新抗原的mRNA装载DC，这允许快速生产并且适合个性化制备。细胞穿透肽（CPP）正在成为一种生物递送系统，其中带负电荷的核酸可以缠绕在阳离子CPP主链上以形成纳米级复合物。这种制备方法有助于标准化。如果DC能够高水平表达和呈递新抗原mRNA，那么它具有很有前景的应用潜力。在本研究中，我们使用来自小鼠结肠癌（MC38）的候选新抗原开发了一种新抗原-mRNA/DC疫苗，并检测了其免疫和抗肿瘤作用。结果表明，新抗原-mRNA/DC疫苗诱导了强烈的T细胞免疫反应，并表现出显著的抗肿瘤作用，有效预防了肿瘤生长。我们的研究为进一步优化DC疫苗的制备并降低其成本提供了实验依据。
