Evaluation of translational potential of mRNA vaccine candidate antigens for pancreatic cancer: a systematic review based on clinical evidence and stratified prioritization strategies

Pancreatic cancer is a highly aggressive malignancy with a 5-year relative survival rate of only 13%. Current treatment options have limited efficacy, and mRNA vaccines offer a new direction for its treatment.

However, how to accurately identify antigen targets that possess tumor specificity, functional relevance, and immunogenicity remains the key bottleneck restricting the clinical translation of mRNA vaccines for pancreatic cancer. Recent clinical studies have advanced KRAS mutant vaccines and personalized neoantigen mRNA vaccines, yet most rely on single antigens or highly individualized designs, limiting scalability and broader clinical applicability.

In this systematic review, we integrated evidence from public databases and experimental studies to identify and evaluate 16 potential pancreatic cancer mRNA vaccine antigens (ADAM9, WNT7A, TMOD3, MET, EFNB2, TPX2, AGPS, OSBPL9, KDM5A, NRAS, SCP-1, GAGE, RAB5A, ANO6, CHMP2B, and PAK2). All candidates were initially selected based on aberrant tumor expression and further prioritized using stratification strategies incorporating antigen-presenting cell infiltration, immune-related cell death pathways such as ferroptosis and pyroptosis, and functional relevance to tumor progression.