Injectable host-guest gel nanovaccine for cancer immunotherapy against melanoma

Abstract

Despite the extensive development of peptide-based tumor antigen vaccines, the field still faces up enormous challenges from lacking clinical efficacy. Here, we report the design and development of a therapeutic nanovaccine for cancer immunotherapy by using gold nanoparticle (AuNPs)-conjugated peptides for incorporation with a supramolecular hydrogel, and via the featured host-guest interactions to carry and deliver select antigen peptides in conjunction with unmethylated cytosine-guanine oligodeoxynucleotide (CpG). The injectable nanovaccine shows significant improvement on the spatial draining lymph nodes (dLNs) delivery of the antigen peptides in antigen presenting cells (APCs) in vivo. Administration of the hydrogel nanovaccine results in a remarkable enhancement of the peptide uptake by APCs in the dLNs with a subsequent induction of the antigen-specific cytotoxic T lymphocytes (CTL) in the periphery, which is in association with 4 to 8-fold increases of these CTLs infiltrating in the tumor tissues. Finally, vaccination with the AuNPs-featured OVAp hydrogel presents with significant retardation of tumor progression that improves the survival rates in mice bearing established B16-OVA melanoma, indicating good efficacy in treating malignant cancers. Together, these findings offer a new strategy for development of spatiotemporally efficient antigen-peptide therapeutic nanovaccine for cancer immunotherapy.

Keywords

• Cancer immunotherapy
• Antigen peptides
• Nanovaccine
• Antigen cross-presentation
• Host-guest hydrogel