Researchers here discuss the application of lipid nanoparticle delivery of messenger RNA as a basis for the development of cancer vaccines. As is the case for vaccines against infectious disease, there are many different ways to provoke an immune response to cancer-specific antigens. Use of messenger RNA to express the desired antigen is the most recent of these technologies. A great of effort has gone into the development of cancer vaccines over the years, and thus it seems likely that a wide range of messenger RNA cancer vaccines will be developed. As yet, however, little of this past effort has resulted in regulatory approval of cancer vaccines and use in the clinic. That low success rate may or may not change with the introduction of messenger RNA as an approach, time will tell.
The landscape of cancer immunotherapy has been redefined by mRNA vaccines as rapid clinically viable strategies that help induce potent, tumor-specific immune responses. This review highlights the current advances in mRNA engineering and antigen design to establish an integrated immunological framework for cancer vaccine development.
Achieving durable clinical benefit requires more than antigen expression. Effective vaccines need precise epitope selection, optimized delivery systems, and rigorous immune monitoring. The field is shifting from merely inducing immune responses to focusing more on the biochemistry and molecular design principles that combine magnitude, polyfunctionality, and longevity to overcome tumor-induced immune suppression.
We examine an integrated immunological framework for mRNA cancer vaccine development, examining how rational molecular engineering of vaccine components, from nucleoside modifications and codon optimization to untranslated regions and linker sequences, shapes immunogenicity and therapeutic efficacy. Future directions will depend on balancing combinatorial strategies combining vaccination with immune checkpoint inhibitors and adoptive cell therapies.
