Engineered virus-mimicking nanovaccine with lymph node–tumor dual-targeting and STING-activating capacity for robust cancer immunotherapy

Zhongjie Wang, Shujun Liu, Ruiqi Ming, Weiwei Wang, Chenguang Wang, Chuyu Li, Jiahua Yang, Fan Zhang*, Guihong Lu, Lin Mei, Li Li Huang

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

摘要

Cancer vaccines have garnered considerable interest for cancer immunotherapy. However, their effectiveness is limited by inadequate proliferation, activation, and tumor infiltration of cytotoxic T lymphocytes (CTLs). Inspired by the potent immunostimulatory properties of viral components and the exposure of calreticulin during immunogenic cell death (ICD) triggered by viral infections; in this study, we describe cGAMP@vEVs, a virus-mimicking nanovaccine strategy by engineering tumor cell-derived extracellular vesicles through virus infection, which co-load both personalized and broad antigen repertoire as well as multiple immune adjuvants to potently elicit antitumor immunity. We demonstrate that cGAMP@vEVs exhibit both the commendable lymph node–tumor dual-targeting and stimulator of interferon genes (STING) pathway-activating capacity, which drive the proliferation and activation of tumor-specific CD8+ T cells in lymph nodes. Simultaneously, cGAMP@vEVs actively accumulate to tumor sites, and ameliorate immunosuppression tumor microenvironment, promoting the spontaneous tumor infiltration of CTLs. The coactivation of the immune response and TME reinitiate the self-sustaining cycle of cancer immunity, therefore efficiently inhibiting tumor progression, metastasis, and recurrence.

源语言英语
页(从-至)416-427
页数12
期刊Journal of Controlled Release
378
DOI
出版状态已出版 - 10 2月 2025

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引用此

Wang, Z., Liu, S., Ming, R., Wang, W., Wang, C., Li, C., Yang, J., Zhang, F., Lu, G., Mei, L., & Huang, L. L. (2025). Engineered virus-mimicking nanovaccine with lymph node–tumor dual-targeting and STING-activating capacity for robust cancer immunotherapy. Journal of Controlled Release, 378, 416-427. https://doi.org/10.1016/j.jconrel.2024.12.034