Personalized Cancer Immunotherapy via Transporting Endogenous Tumor Antigens to Lymph Nodes Mediated by Nano Fe3 O4

Abstract

While immunotherapy has a tremendous clinical potential to combat cancer, immune responses generated by conventional cancer immunotherapy remain not enough to completely eliminate tumors, mainly due to the tumor's immunosuppressive microenvironment and heterogeneity of tumor immunogenicity. To improve antitumor immune responses and realize personalized immunotherapy, in this report, endogenous tumor antigens (ETAs) that dynamically present on tumor cells are transported to lymph nodes (LNs). Based on the hypothesis that nano Fe₃ O₄ (≈10 nm) could serve as the nanocarrier for transporting ETAs from the tumor to LNs, we wondrously find that Fe₃ O₄ has a tremendous potential to improve cancer immunotherapy, because of its excellent protein-captured efficiency and LNs-targeted ability. To ensure the optimal ETAs-bound efficiency of Fe₃ O₄ , a core-shell formulation (denoted as Ce6/Fe₃ O₄ -L) is developed and specific release of Fe₃ O₄ in tumor is enabled. These findings provide a simple and general strategy for boosting cytotoxic T-cell response and realizing personalized cancer immunotherapy simultaneously.

Keywords: endogenous tumor antigens; immunosuppressive microenvironment; lymph nodes; nano Fe3O4; personalized immunotherapy.