Nanoshield Architecture Harnessing Neoantigen-Targeting Peptides Enables Durable Post-surgical Glioma Immunotherapy.

Abstract

Despite advances in immunotherapy, its efficacy against postoperative glioma recurrence remains limited. Here, we present a neoantigen-targeting peptide nanoshield that synergizes with glioma resection to eliminate residual tumor cells and prevent relapse. The nanoshield architecture is constructed using a multicationic protein (MCP) as the structural scaffold, which is assembled with the mutated isocitrate dehydrogenase 1 (muIDH1) neoantigen. The nanoshield vaccine enables lysosome-escaping muIDH1 delivery and inflammasome-mediated immune activation, generating polyfunctional CD8⁺ T cells. The results demonstrate superior and durable immunogenicity, with a 3-fold increase in CD8⁺ T cells and a 6-fold in vivo retention profile compared to free peptide controls, respectively. This leads to significant reduction in tumor size in prophylactic and therapeutic glioma models. Notably, it achieves over 40% improvement in terms of postoperative recurrence-free survival through combining the nanovaccine with antiprogrammed death-1 (aPD-1) therapy. Our immunotherapeutic strategy induces potent antitumor immunity, offering promising clinical potential for postoperative management.