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用gasdermin E武装溶瘤M1病毒可增强乳腺癌的抗肿瘤疗效。

Arming oncolytic M1 virus with gasdermin E enhances antitumor efficacy in breast cancer.

作者信息

Chen Xiao-Yu, Liu Ying, Zhu Wen-Bo, Li Shu-Hao, Wei Song, Cai Jing, Lin Yuan, Liang Jian-Kai, Yan Guang-Mei, Guo Li, Hu Cheng

机构信息

Departments of Pharmacology, Sun Yat-sen University, No. 074, Zhongshan Second Road, Guangzhou 510080, China.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, Guangdong 510630, China.

出版信息

iScience. 2024 Oct 16;27(11):111148. doi: 10.1016/j.isci.2024.111148. eCollection 2024 Nov 15.

DOI:10.1016/j.isci.2024.111148
PMID:39555415
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11565026/
Abstract

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.

摘要

由gasdermin蛋白（GSDM）的N端结构域驱动的细胞焦亡，通过将淋巴细胞吸引至肿瘤微环境（TME）来促进抗肿瘤免疫。然而，目前的细胞焦亡诱导疗法，如药物注射和光疗，仅限于局部治疗，不适用于广泛或微小的转移性病变。本研究构建了溶瘤M1病毒（rM1-mGSDME_FL和rM1-mGSDME_NT），以选择性地将GSDME递送至肿瘤细胞。这些修饰病毒在乳腺癌模型中增强了肿瘤细胞死亡，抑制了肿瘤生长，延长了小鼠生存期，并促进了免疫细胞浸润，通过诱导细胞焦亡显示出显著的抗癌潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/34b6e419c967/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/021d1da49549/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/eea283c32f97/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/bc9b959c93ff/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/13eddf007f91/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/34b6e419c967/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/021d1da49549/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/eea283c32f97/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/bc9b959c93ff/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/13eddf007f91/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/11565026/34b6e419c967/gr4.jpg

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本文引用的文献

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Oncolytic virus-based combination therapy in breast cancer.基于溶瘤病毒的乳腺癌联合治疗。
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PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment.PD-1 和 PD-L1：免疫交响乐的建筑师和癌症治疗免疫疗法突破的推动者。
精准医学时代的乳腺癌治疗
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Engineered Macrophages Tune Intratumoral Cytokines through Precisely Controlled Self-Pyroptosis to Enhance Bladder Cancer Immunotherapy.工程化巨噬细胞通过精确控制的自细胞焦亡来调节肿瘤内细胞因子，增强膀胱癌免疫治疗。
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