A redox-responsive nanovaccine for cytosolic delivery of antigen and adjuvant to enhance cancer immunotherapy

Cancer vaccines have garnered significant attention in cancer immunotherapy because they trigger tumor-specific immune responses. However, their effectiveness is hindered by inefficient antigen and adjuvant delivery at the subcellular level, which is essential to stimulate a robust CD8+ T cell response. This study presents PAR/OVA, a cancer nanovaccine developed by combining imiquimod (R837)-modified polyamidoamine dendrimers with the model protein antigen ovalbumin (OVA). Within the nanovaccine, R837 is an adjuvant for the Toll-like receptor 7 (TLR7) pathway and a structural component that facilitates OVA loading. In dendritic cells (DCs), the high cytoplasmic glutathione levels triggered the breakdown of PAR/OVA, releasing OVA and R837, which induced DC activation and antigen cross-presentation. Furthermore, PAR/OVA vaccination showed a protective effect and effectively inhibited B16-OVA tumor progression, indicating its potential in cancer immunotherapy. Combining this vaccine with an immune checkpoint blockade enhanced antitumor efficacy by improving the ability of cytotoxic T lymphocytes to target cancer cells within the tumor microenvironment. These findings underscore the potential of this adjuvant/antigen-delivering nanovaccine in cancer immunotherapy.