Cancer cell membrane proteins-encapsulated nanovaccine enhances cancer immunotherapy and prevention by provoking antigen-specific cellular immunity via the dendritic cell-targeted delivery

Abstract

Cancer nanovaccines offer a promising strategy for fighting against tumors, however, the engineering of cancer nanovaccines that can be easily fabricated with tanglesome cancer cell-derived antigens and elicit an adequately strong tumor-specific cellular immunity remains challenging. Herein, metal-phenolic networks (MPNs) are used as an antigen delivery platform to prepare the mannose-modified MPNs nanovaccine loaded with ovalbumin (OVA) and the immunoadjuvant CpG oligodeoxynucleotide (MMOC) through the facile self-assembly. When the model antigen OVA is substituted with cancer cell membrane proteins (CCMPs), the nanovaccine is called MMCC. MMOC markedly activates dendritic cells (DCs) via the mannose-mediated endocytosis and efficiently promotes the antigen cross-presentation, thus inspiring a robust antigen-specific CD8+ T cell response as well as immune memory effect in vivo. Consequently, MMOC exhibits admirable therapeutic and preventive results on E.G7-OVA tumors. Moreover, the combination use of MMCC with anti-PD1 significantly inhibits the growth of 4T1 tumors by strengthening the cellular immunity and decreasing the proportion of regulatory T cells (Tregs). The survival rate of 4T1 tumor-bearing mice in the prophylaxis assay is maintained at 100 % by MMCC over 42 days. Altogether, this study affords a universal and effective nanovaccine preparation strategy for cancer immunotherapy and prevention.