Systematic review identifies 16 mRNA vaccine antigens for pancreatic cancer immunotherapy

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. ADAM9 and PAK2 showed high expression in pancreatic cancer and strong associations with tumor proliferation, invasion, and immune regulation. SCP-1 and GAGE, as cancer–testis antigens, exhibited high tumor specificity and immunogenic potential. In addition, KDM5A and ANO6 may enhance antitumor efficacy through modulation of ferroptosis or pyroptosis. Nevertheless, several candidates remain constrained by normal tissue expression or limited mechanistic evidence. This review provides a stratified framework for antigen prioritization and highlights key challenges in pancreatic cancer mRNA vaccine development, offering guidance for future multi-antigen vaccine design and translational immunotherapy.