Metabolically glycoengineered vesicular nanovaccine for direct antigen presentation and robust cancer immunotherapy

Dendritic cell (DC) vaccines have made substantial progress in cancer immunotherapy; however, their efficacy is still limited by the transient in vivo fate of mature DCs and suboptimal lymphatic transport. Here, we report a metabolically glycoengineered, nanovesicle-based and personalized nanovaccine (GSNVs) that displays upregulated C-C chemokine receptor 7 (CCR7) and major histocompatibility (MHC)-I complexes to promote lymph node homing and effectively presents tumor antigens to CD8⁺ T cells, ultimately triggering a strong antigen-specific antitumor immune response. GSNVs were generated from ManNAc-engineered bone marrow-derived DCs (BMDCs) pulsed with highly immunogenic exosomes derived from senescent tumor cells. Metabolic glycoengineering endows BMDCs with enhanced antigen cross-presentation, elevated CCR7 expression, and negligible PD-L1 levels, thereby promoting robust and persistent CD8⁺ T cell responses. Notably, GSNVs treatment elicits robust antitumor immunity, rescues T cell exhaustion, and markedly inhibits tumor growth of B16-OVA-bearing mice. Collectively, these results reveal that our metabolically glycoengineered GSNVs could be an effective strategy to overcome the inherent limitation of DC vaccines in inducing adaptive antitumor immunity for its potential application in personalized cancer immunotherapy.