mRNA Cancer Vaccines: From Pandemic Paradigm to Personalized Oncology Therapeutics

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.