Ferritin nanoparticle-based SpyTag/SpyCatcher-enabled click vaccine for tumor immunotherapy.

Recently， tumor neoantigens have been attractive for development of personal therapeutic vaccines. However， how to instantly deliver multiple neoantigens for efficient anti-tumor immunity is still challenging. Here， we established a SpyCatcher-modified ferritin nanoparticle platform， which permits convenient and stable covalent conjugation with tumor specific antigens containing SpyTag in a click-link manner. These ferritin nanoparticles are rapidly drained to lymph nodes and target dendritic cells， especially CD8α population， upon subcutaneous immunization. Ferritin nanoparticles carrying HPV16 oncogene E7 peptide antigen or MC38 tumor derived mutant neoantigens elicit about 2-3 folds enhanced antigen-specific cytotoxic T lymphocyte (CTL) response than soluble peptide antigens and significantly suppress the growth of E7-related or MC38 tumors. The anti-tumor effect was further enhanced in combination with PD-1 checkpoint blockade. Together， our study provides a ferritin nanoparticle-based， SpyTag/SpyCatcher-enabled click vaccine platform， especially for personalized tumor immunotherapy.