Xiao-Yu Chen, Ying Liu, Wen-Bo Zhu, Shu-Hao Li, Song Wei, Jing Cai, Yuan Lin, Jian-Kai Liang, Guang-Mei Yan, Li Guo, Cheng Hu
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Arming oncolytic M1 virus with gasdermin E enhances antitumor efficacy in breast cancer.
Pyroptosis, driven by the N-terminal domain of gasdermin proteins (GSDM), promotes antitumor immunity by attracting lymphocytes to the tumor microenvironment (TME). However, current pyroptosis-inducing therapies like drug injections and phototherapy are limited to localized treatments, making them unsuitable for widespread or microscopic metastatic lesions. This study engineered oncolytic M1 viruses (rM1-mGSDME_FL and rM1-mGSDME_NT) to selectively deliver GSDME to tumor cells. These modified viruses enhanced tumor cell death in breast cancer models, suppressed tumor growth, extended survival in mice, and boosted immune cell infiltration, demonstrating significant anticancer potential through pyroptosis induction.
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