Limitation
Cancer vaccine development is challenging because cancer-derived neoantigens are difficult to distinguish from normal proteins, making immune response induction difficult, and there is no comparison or benchmarking between modalities (mRNA, peptide, DNA, etc.). The core problem is that the process of accurately predicting and presenting neoantigens and verifying their interaction with T-cell receptors (TCRs) is extremely complex, with prediction algorithms having immunogenicity hit rates of less than 5%.
Conclusion
Tumor heterogeneity and preclinical indicators alone make it difficult to guarantee actual tumor removal effects, making surface expression verification (immunopeptotyping) and functional screening (single-cell TCR sequencing, etc.) essential. Future challenges include reducing the cost of personalized mRNA manufacturing (approximately $150,000) and manufacturing complexity through microfluidics and cell-free synthesis technologies, as well as developing preventive vaccines targeting broad common antigens.