Biomimetic Dendritic\nCell-Based Nanovaccines for Reprogramming\nthe Immune Microenvironment to Boost Tumor Immunotherapy

Although dendritic cell (DC)-mediated immunotherapies\nare effective\noptions for immunotherapy, traditional DC vaccines are hampered by\na variety of drawbacks such as insufficient antigen delivery, weak\nlymph node homing, and the risk of living cell transfusion. To address\nthe above-mentioned issues, we developed a personalized DC-mimicking\nnanovaccine (HybridDC) that enhances antigen presentation and elicits\neffective antitumor immunity. The biomimetic nanovaccine contains\ncell membranes derived from genetically engineered DCs, and several\ncellular components are simultaneously anchored onto these membranes,\nincluding CC-chemokine receptor 7 (CCR7), tumor-associated antigenic\n(TAA) peptide/tumor-derived exosome (TEX), and relevant costimulatory\nmolecules. Compared with previous vaccines, the HybridDC vaccine showed\nan increased ability to target lymphoid tissues and reshape the immune\nlandscape in the tumor milieu. HybridDC demonstrated significant therapeutic\nand prophylactic efficacy in poorly immunogenic, orthotopic models\nof glioma. Furthermore, the HybridDC vaccine potentiates the therapeutic\nefficacy of immune checkpoint blockade (ICB) therapy, providing a\npotential combination strategy to maximize the efficacy of ICB. Specifically,\nHybridDC can induce long-term protective immunity in memory T cells.\nOverall, the HybridDC vaccine is a promising platform for personalized\ncancer vaccines and may offer a combinational modality to improve\ncurrent immunotherapy.