Adjuvanted RNA Origami-A Tunable Peptide Assembly Platform for Constructing Cancer Nanovaccines.

BACKGROUND/

objectivesCancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as vaccine carriers to incorporate both adjuvants and peptides. One such nanoparticle is RNA origami (RNA-OG), a nucleic acid nanostructure that is programmed to form different sizes and shapes. Our designed RNA-OG can incorporate various biomolecules and has intrinsic adjuvant activity by acting as a toll-like receptor 3 agonist. We previously showed that the RNA-OG functions as an adjuvanted, carrier-free vaccine platform to assemble peptides. Although effective, only a fixed number of peptides (13) could be covalently linked to each RNA-OG.

methodsHere, we developed a simple physical assembly strategy to attach polylysine-linked neopeptides onto RNA-OG so that the number of peptides per RNA-OG could be readily tuned and tested for their immunogenicity.

resultsAlthough the vaccines with a high number of peptides, i.e., 100-200 peptides/RNA-OG, led to greater peptide presentation by bone marrow-derived dendritic cells, they failed to mount effective CD8

conclusionsOur findings have significant implications for peptide vaccine design regarding peptide dosages and structural stability of RNA-OG complexed with peptides, which could guide the development of more effective peptide vaccines for cancer immunotherapy.