mRNA cancer vaccines: delivery strategies, immune modulation, and clinical translation.

Cancer remains a major global health challenge, and traditional treatments often involve significant toxicity and limited benefits for patients with advanced-stage disease. mRNA vaccines have recently emerged as a promising approach in cancer immunotherapy due to their flexibility in design, rapid production, and suitability for personalized treatment. This review summarizes the molecular basis, main classifications, and mechanisms of action of mRNA vaccines for cancer therapy and systematically discusses progress in strategies for delivering tumor-specific antigens, tumor-associated antigens, and immunomodulatory factors. Special attention is given to advances in delivery technologies, especially lipid nanoparticle (LNP) systems, and their potential applications across various cancers. We suggest that the effectiveness of mRNA cancer vaccines depends not only on selecting the right antigens but also on delivery methods that modulate the immune response and reshape the tumor microenvironment. Melanoma is a prime candidate for prioritizing the research and development of mRNA cancer vaccines, given the current clinical landscape. Furthermore, major challenges that continue to limit progress include insufficient stability, suboptimal delivery efficiency, uncontrolled immunogenicity, and the difficulty of overcoming tumor heterogeneity. This review aims to serve as a useful reference for further development and clinical translation of mRNA cancer vaccines.