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.
Authors
- Jiankai Liang (ORCID: https://orcid.org/0000-0002-4378-7646)
- Cheng Hu (ORCID: https://orcid.org/0000-0001-7554-3438)
- S. Li (ORCID: https://orcid.org/0009-0003-4100-987X)
- Jing Cai (ORCID: https://orcid.org/0000-0003-4128-572X)
- Wei Song (ORCID: https://orcid.org/0000-0003-3756-198X)
- Xiaoyu Chen (ORCID: https://orcid.org/0000-0003-2203-233X)
- Guangmei Yan (ORCID: https://orcid.org/0000-0002-8822-2657)
- Ying Liu (ORCID: https://orcid.org/0000-0001-5868-3447)
- Wenbo Zhu (ORCID: https://orcid.org/0000-0002-9143-5733)
- Lin Yuan (ORCID: https://orcid.org/0000-0001-8013-4313)
- Li Guo (ORCID: https://orcid.org/0000-0003-1494-0717)
Institutions
- Ministry of Education of the People's Republic of China (CN)
- Sun Yat-sen University (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Sun Yat-sen University Cancer Center (CN)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
Publication Details
- Journal
- iScience
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1016/j.isci.2024.111148
- Citations
- 6
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 3.30
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province
- Guangzhou Municipal Science and Technology Project
- National Key Research and Development Program of China Stem Cell and Translational Research
- Basic and Applied Basic Research Foundation of Guangdong Province