Development of mRNA Cancer Vaccines: Delivery Strategies and Immunogenicity Optimization

Dec 8, 2025Current medical science

Creating mRNA Cancer Vaccines: How to Deliver Them and Boost Immune Response

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Abstract

mRNA vaccines may offer significant advantages in oncology, including rapid development and safety.

Clinical translation of mRNA vaccines faces challenges like instability and inefficient delivery.
Advancements in molecular design include both non-replicating and self-amplifying RNAs.
Lipid nanoparticles (LNPs) have been identified as effective delivery strategies to enhance stability and immune response.
Different administration routes may influence the strength of antitumor immunity.
The review categorizes antigens as viral, tumor-associated, and neoantigens, highlighting their roles in vaccine effectiveness.
Innovative uses of mRNA to encode immunomodulators may help reprogram the immunosuppressive tumor microenvironment.

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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.

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Development of mRNA Cancer Vaccines: Delivery Strategies and Immunogenicity Optimization

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