mRNA-based cancer vaccines: A new frontier in personalized immunotherapy

The advancement of mRNA technology has rejuvenated the cancer treatment immunotherapy field by providing a flexible and scalable platform to generate tumor-associated or patient-specific neoantigens, which induces strong cytotoxic and helper T-cell outcomes and also immunologically stimulates innate immunity in the body at the same time. In contrast to conventional vaccines, mRNA preparations are non-integrative, safe, and scalable, allowing personalization of mutational landscape-based vaccines much faster due to the unique mutations of tumors in individuals. Early clinical trials in melanoma, breast, glioblastoma, and pancreatic cancer have revealed encouraging immunogenicity results, especially when used along with checkpoint inhibitors or other complementary therapies. The recent news of discovering the mRNA cancer vaccine, Enteromix, in Russia, also points to the potential of the translation and the global trend of this technology, which is both effective in treatment and accessible in clinical practice. Although the issues such as heterogeneity of the tumors, antigen escape, delivery efficiency, and manufacturing logistics are present, the development of artificial intelligence, multi-omics integration, and next-generation delivery systems will address these challenges. This review gives an overview of the concepts and principles, types, delivery mechanisms, clinical applications, and future perspective of mRNA-based cancer vaccines with a focus to its revolutionary contribution to personalized oncology and the overall next-generation immunotherapy.