Arming oncolytic M1 virus with gasdermin E enhances antitumor efficacy in breast cancer
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
Affiliations
Xiao-yu Chen
Departments of Pharmacology, Sun Yat-sen University, No. 074, Zhongshan Second Road, Guangzhou 510080, China
Ying Liu
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong 510630, China
Wen-bo Zhu
Departments of Pharmacology, Sun Yat-sen University, No. 074, Zhongshan Second Road, Guangzhou 510080, China
Shu-hao Li
Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong 510630, China
Song Wei
Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong 510630, China
Jing Cai
Departments of Pharmacology, Sun Yat-sen University, No. 074, Zhongshan Second Road, Guangzhou 510080, China
Yuan Lin
Departments of Pharmacology, Sun Yat-sen University, No. 074, Zhongshan Second Road, Guangzhou 510080, China; Advanced Medical Technology Center, The First Affiliated Hospital-Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Human Microbiome and Elderly Chronic Diseases, Ministry of Education, Guangzhou, China
Jian-kai Liang
Departments of Pharmacology, Sun Yat-sen University, No. 074, Zhongshan Second Road, Guangzhou 510080, China
Guang-mei Yan
Departments of Pharmacology, Sun Yat-sen University, No. 074, Zhongshan Second Road, Guangzhou 510080, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Li Guo
Departments of Pharmacology, Sun Yat-sen University, No. 074, Zhongshan Second Road, Guangzhou 510080, China; Corresponding author
Cheng Hu
Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong 510630, China; Corresponding author
Summary: 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.
