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 Th1-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.
Keywords: Cancer vaccines; Dendritic cells; IL-10; Immunotherapy; Melanoma.
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