Biomimetic Dendritic Cell-Based Nanovaccines for Reprogramming the Immune Microenvironment to Boost Tumor Immunotherapy

免疫疗法 免疫系统 树突状细胞 抗原呈递 癌症研究 癌症免疫疗法 抗原 肿瘤微环境 免疫学 嵌合抗原受体 T细胞 获得性免疫系统 抗原提呈细胞 生物 医学
作者
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 Li,Wei Li,Yingqi Zhang,Qingdong Guo,Meng Li,Jintao Gu
出处
期刊:ACS Nano [American Chemical Society]
标识
DOI:10.1021/acsnano.4c09653
摘要

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.
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