Development of mRNA Cancer Vaccines: Delivery Strategies and Immunogenicity Optimization

mRNA vaccines have emerged as a transformative platform in oncology, offering significant advantages in rapid development, flexibility, and safety over traditional modalities. However, their clinical translation faces challenges such as mRNA instability, inefficient in vivo delivery, and the immunosuppressive tumor microenvironment (TME). This review comprehensively outlines recent advancements in overcoming these hurdles. We discuss the molecular design of mRNA vaccines, including non-replicating and self-amplifying RNAs, and highlight breakthroughs in delivery strategies, particularly lipid nanoparticles (LNPs), that enhance stability and immunogenicity. Furthermore, we explore various administration routes and their impact on eliciting robust antitumor immunity. The review also covers the classification of antigens-viral, tumor-associated, and neoantigens-and the innovative use of mRNA to encode immunomodulators to reprogram the TME. Finally, we address key considerations for clinical translation, including manufacturing, stability, safety, and combination strategies with immunotherapies. By synthesizing these developments, this review underscores the potential of mRNA vaccines to realize personalized cancer immunotherapy and outlines future directions for the field.