Neoantigen mRNA vaccines have progressed from experimental constructs to clinically evaluated immunotherapies grounded in tumor genomics and modular RNA engineering. By encoding tumor-restricted antigens, these platforms aim to induce targeted T-cell responses while minimizing off-target toxicity. Early clinical studies, particularly in melanoma and non-small cell lung cancer, demonstrate that personalized and hybrid vaccine strategies can expand tumor-reactive T-cell clones and improve recurrence-free outcomes when combined with immune checkpoint blockade. However, challenges including manufacturing timelines, HLA diversity, tumor heterogeneity, and immune editing limit broad implementation. Recent advances in antigen prioritization algorithms, transcript design, and delivery platforms have improved translational feasibility and reduced production variability. Shared and off-the-shelf approaches targeting recurrent driver mutations offer scalable alternatives, while adaptive strategies incorporating ctDNA monitoring raise the possibility of dynamic vaccine updating during treatment. Integration with immune-modulating therapies and rational clinical positioning, particularly in adjuvant and minimal residual disease settings, are likely to define near-term success. Collectively, neoantigen mRNA vaccination represents a flexible therapeutic framework rather than a single platform. Its long-term impact will depend on aligning molecular engineering, immune calibration, manufacturing scalability, and regulatory adaptation to achieve durable clinical.
Li et al. (Wed,) studied this question.