Recombinant ferritin-based nanoparticles as neoantigen carriers significantly inhibit tumor growth and metastasis

Background Tumor neoantigen peptide-based vaccines, systemic immunotherapies that enhance antitumor immunity by activating and expanding antigen-specific T cells, have achieved remarkable results in the treatment of a variety of solid tumors. However, how to effectively deliver neoantigens to induce robust antitumor immune responses remains a major obstacle. Results Here, we developed a safe and effective neoantigen peptide delivery system (neoantigen-ferritin nanoparticles, neoantigen-FNs) that successfully achieved effective lymph node targeting and induced robust antitumor immune responses. Genetically engineered self-assembled particles with a size of 12 nm were obtained by fusing a neoantigen with optimized ferritin, which rapidly migrates to and continuously accumulates in lymph nodes. The neoantigen-FNs vaccine induced a greater quantity and quality of antigen-specific CD8 ⁺ T cells and resulted in significant growth control of multiple tumors, dramatic inhibition of melanoma metastasis and regression of established tumors. In addition, no obvious toxic side effects were detected in the various models, indicating the high safety of optimized ferritin as a vaccine carrier. Conclusions Homogeneous and safe neoantigen-FNs could be a very promising system for neoantigen peptide delivery because of their ability to efficiently migrate to lymph nodes and induce efficient antitumor immune responses.