Bo Yang, Juan Liu, Li Yang, Xiaoxuan Liu
The groundbreaking success of messenger RNA (mRNA) vaccines during the COVID-19 pandemic has significantly accelerated their application in oncology. This review comprehensively synthesizes the recent advancements in mRNA cancer vaccine development, emphasizing three critical domains: mechanistic innovations, clinical translation, and ongoing challenges. Technologically, advancements in nucleotide modification, lipid nanoparticle (LNP) delivery systems, and AI-driven neoantigen selection have significantly improved vaccine stability, immunogenicity, and personalization. Clinically, more than 150 trials have demonstrated the synergistic efficacy of mRNA vaccines (e.g., mRNA-4157/V940, BNT122) in combination with immune checkpoint inhibitors (ICIs), particularly in melanoma, with Phase III trials currently underway. Individualized neoantigen vaccines targeting patient-specific mutations have shown unprecedented response rates (> 50% in certain cohorts), while shared-antigen vaccines are progressing for high-incidence cancers. However, several critical challenges remain: (1) overcoming immunosuppressive tumor microenvironments (TME), (2) addressing systemic toxicities and LNP-related limitations, (3) scaling up cost-effective personalized manufacturing, and (4) optimizing targeted delivery. Future research directions encompass self-amplifying mRNA constructs, novel biomaterial vectors, neoadjuvant applications, and multi-omics integration for next-generation vaccine development. With rapid industrialization and evolving regulatory frameworks, mRNA vaccines are well-positioned to revolutionize precision cancer immunotherapy despite persistent translational barriers.