Kirtane Ameya R, Traverso Giovanni
Department of Pharmaceutics, University of Minnesota, Minneapolis, MN.
Department of Mechanical Engineering, Massachusetts Institute of Technology.
Cancer J. 2025;31(2). doi: 10.1097/PPO.0000000000000764. Epub 2025 Mar 27.
mRNA vaccines consist of antigen-encoding mRNA, which produces the antigenic protein upon translation. Coupling antigen production with innate immune activation can generate a potent, antigen-specific T-cell response. Clinical reports have demonstrated the ability of mRNA vaccines to elicit an anticancer immune response against various tumor types. Here, we discuss strategies to enhance the potency of mRNA vaccines. We provide an overview of existing knowledge regarding the activation and trafficking mechanisms of mRNA vaccines and share optimization strategies to boost mRNA-mediated antigen production. In addition, we address methods to target mRNA vaccines to dendritic cells and lymph nodes, key initiators of the immune response. Finally, we review strategies for enhancing immune activation using adjuvants compatible with mRNA vaccines. mRNA vaccines offer unique advantages that can be utilized for oncology applications. However, significant work is needed to understand their underlying mechanisms and develop technologies to improve their effectiveness.
信使核糖核酸（mRNA）疫苗由编码抗原的mRNA组成，该mRNA在翻译时产生抗原性蛋白质。将抗原产生与先天免疫激活相结合可产生强大的、抗原特异性的T细胞反应。临床报告已证明mRNA疫苗能够引发针对各种肿瘤类型的抗癌免疫反应。在此，我们讨论增强mRNA疫苗效力的策略。我们概述了关于mRNA疫苗激活和运输机制的现有知识，并分享增强mRNA介导的抗原产生的优化策略。此外，我们阐述了将mRNA疫苗靶向树突状细胞和淋巴结（免疫反应的关键启动者）的方法。最后，我们回顾了使用与mRNA疫苗兼容的佐剂增强免疫激活的策略。mRNA疫苗具有可用于肿瘤学应用的独特优势。然而，需要开展大量工作来了解其潜在机制并开发提高其有效性的技术。
