TY - JOUR
T1 - Engineered virus-mimicking nanovaccine with lymph node–tumor dual-targeting and STING-activating capacity for robust cancer immunotherapy
AU - Wang, Zhongjie
AU - Liu, Shujun
AU - Ming, Ruiqi
AU - Wang, Weiwei
AU - Wang, Chenguang
AU - Li, Chuyu
AU - Yang, Jiahua
AU - Zhang, Fan
AU - Lu, Guihong
AU - Mei, Lin
AU - Huang, Li Li
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2025/2/10
Y1 - 2025/2/10
N2 - 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.
AB - 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.
KW - Dual-targeting
KW - STING agonist
KW - Tumor microenvironment
KW - cancer immunotherapy
KW - cancer vaccine
UR - http://www.scopus.com/inward/record.url?scp=85212432798&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2024.12.034
DO - 10.1016/j.jconrel.2024.12.034
M3 - Article
AN - SCOPUS:85212432798
SN - 0168-3659
VL - 378
SP - 416
EP - 427
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -