Biomimetic Dendritic Cell-Based Nanovaccines for Reprogramming the Immune Microenvironment to Boost Tumor Immunotherapy
Weizhong Wang, Cheng Zou, Xiao Liu, Lei He, Zhengcong Cao, Maorong Zhu, Yuxin Wu, Xiaolin Liu, Jiying Ma, Y Wang, Yile Zhang, Kuo Zhang, Shuning Wang, Wangqian Zhang, Wei Liu, Wei Lin, Yingqi Zhang, Qingdong Guo, Meng Li, Jintao Gu
Abstract
Although dendritic cell (DC)-mediated immunotherapies are effective options for immunotherapy, traditional DC vaccines are hampered by a variety of drawbacks such as insufficient antigen delivery, weak lymph node homing, and the risk of living cell transfusion. To address the above-mentioned issues, we developed a personalized DC-mimicking nanovaccine (HybridDC) that enhances antigen presentation and elicits effective antitumor immunity. The biomimetic nanovaccine contains cell membranes derived from genetically engineered DCs, and several cellular components are simultaneously anchored onto these membranes, including CC-chemokine receptor 7 (CCR7), tumor-associated antigenic (TAA) peptide/tumor-derived exosome (TEX), and relevant costimulatory molecules. Compared with previous vaccines, the HybridDC vaccine showed an increased ability to target lymphoid tissues and reshape the immune landscape in the tumor milieu. HybridDC demonstrated significant therapeutic and prophylactic efficacy in poorly immunogenic, orthotopic models of glioma. Furthermore, the HybridDC vaccine potentiates the therapeutic efficacy of immune checkpoint blockade (ICB) therapy, providing a potential combination strategy to maximize the efficacy of ICB. Specifically, HybridDC can induce long-term protective immunity in memory T cells. Overall, the HybridDC vaccine is a promising platform for personalized cancer vaccines and may offer a combinational modality to improve current immunotherapy.