mRNA-based cancer vaccines for cancer immunotherapy: current progress, challenges, and emerging opportunities

mRNA-based cancer vaccines have emerged as a promising platform for therapeutic cancer immunotherapy because of their ability to encode tumor-associated antigens, tumor-specific antigens, and patient-specific neoantigens and to induce antigen-specific immune responses. Their flexible and cell-free manufacturing enables rapid adaptation and facilitates the development of personalized vaccines based on individual tumor mutations and HLA profiles. However, the clinical translation of mRNA-based cancer vaccines remains challenging because of difficulties in neoantigen identification, maintaining mRNA stability, achieving efficient intracellular and tissue-specific delivery and endosomal escape, optimizing antigen expression, and overcoming tumor heterogeneity, and immunosuppressive tumor microenvironments. Advances in mRNA engineering, including sequence optimization, modified nucleosides, cap and UTR optimization, and lipid nanoparticle-based delivery, have improved RNA stability, cellular uptake, antigen expression, and immune activation in various experimental and clinical settings. This review discusses the principles of mRNA-based cancer vaccines, strategies for neoantigen identification and vaccine development, mRNA production and formulation, nanoparticle-mediated delivery, major challenges affecting stability, targeting, expression, and immune stimulation, and emerging clinical applications. Particular emphasis is placed on personalized neoantigen vaccines and combination approaches with immune checkpoint inhibitors. Continued integration of RNA engineering, nanotechnology, computational antigen prediction, and precision immunotherapy may enable more effective and clinically adaptable mRNA-based cancer vaccines.