Nanovaccines silencing IL-10 production at priming phase for boosting immune responses to melanoma

Abstract

Despite the significant efforts in developing cancer vaccines, there are still numerous challenges that need to be addressed to ensure their clinical efficacy. Herein, a lymphatic dendritic cell (DC)-targeted artificial nanovaccine mimicking tumor cell membrane (ATM-NV) is developed to boost effector immune response and control immunosuppression simultaneously. The NVs are formulated with lipids, tumor cell membrane proteins, imiquimod (IMQ), and IL-10 siRNA. IL-10 siRNA is incorporated to inhibit the secretion of IL-10, an immunosuppressive cytokine, of maturated DCs upon IMQ. To enhance the DC targeting ability, the nanovaccine surface was non-covalently conjugated with the anti-CD205 antibody. The IMQ and IL-10 siRNA co-loaded, CD205 receptor targeted artificial tumor membrane NVs (IMQ/siR@ATM-NVs) efficiently migrate to the tumor-draining lymph node and target DCs. Furthermore, immunization with IMQ/siR@ATM-NVs reduces the production of IL-10 and increases T(h)1-driven antitumor immunity resulted in a great tumor inhibition efficacy. Our results suggest a potential strategy to promote the vaccination's antitumor efficacy by blocking the intrinsic negative regulators in DCs.