Enhancing cancer vaccine efficacy via electrostatic engineering of an FcγR-targeted protein.

BACKGROUND

Effective cancer vaccines require delivery platforms that can simultaneously enhance immune responses, maintain safety, and simplify the formulation process. This study aimed to develop a novel vaccine delivery system based on the Staphylococcus aureus-derived formyl peptide receptor-like 1 inhibitory protein (FLIPr), which naturally targets Fcγ receptors on antigen-presenting cells.

METHODS

A recombinant variant, rF9R, was engineered by adding nine arginine residues to the C-terminus of FLIPr to facilitate electrostatic binding with anionic components. To optimize this interaction, epitopes were modified with five aspartic acid residues. The platform's ability to form stable complexes with peptides, CpG oligodeoxynucleotides, and protein antigens was evaluated. The efficacy of the rF9R/rE7m complex was subsequently tested in tumor models to assess CD8+ T-cell activation and tumor regression.

RESULTS

The rF9R protein successfully bound peptides and antigens to form stable complexes, significantly enhancing antigen delivery and immune activation. In vivo results demonstrated that the rF9R/rE7m complex-both as a standalone treatment and when combined with CpG-elicited robust CD8+ T-cell responses. This immune activation led to significant tumor regression in the studied models.

CONCLUSION

The rF9R platform functions as both an efficient carrier and a potent immunostimulatory component. By providing a simple and versatile method for delivering peptide and subunit vaccines, rF9R represents a promising strategy for advancing cancer immunotherapy.