Engineered mRNA vaccine targeting immune cells triggers strong anti-cancer response in pancreatic cancer

One-third of mice treated with the exosome-augmented mRNA nanovaccine achieved complete tumor regression.

• Pancreatic ductal adenocarcinoma (PDAC) is associated with KRAS mutations in over 90% of cases.
• The developed mRNA nanovaccine features a series-connected design that condenses five immunodominant KRAS-mutant epitopes into a single open reading frame.
• This design enhances antigen presentation compared to conventional methods that use full-length transcripts.
• The exosome-cloaked lipid nanoparticles facilitate targeted delivery to lymph nodes and activate immune responses.
• The mKRAS SC-LNP@exo treatment led to potent dendritic cell activation and increased CD8⁺ T cell infiltration in a Pan02 tumor model.
• The approach may convert immunologically 'cold' KRAS-mutant PDAC tumors into responsive ones.

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