用gasdermin E武装溶瘤M1病毒可增强乳腺癌的抗肿瘤疗效。

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-10-16 eCollection Date: 2024-11-15 DOI:10.1016/j.isci.2024.111148

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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引用次数: 0

摘要

由gasdermin蛋白（GSDM）N端结构域驱动的热蛋白沉积（Pyroptosis）可通过吸引淋巴细胞进入肿瘤微环境（TME）来促进抗肿瘤免疫。然而，目前的热核素诱导疗法（如药物注射和光疗）仅限于局部治疗，不适合广泛或微小转移病灶。本研究设计了溶瘤 M1 病毒（rM1-mGSDME_FL 和 rM1-mGSDME_NT），以选择性地向肿瘤细胞递送 GSDME。这些改良病毒在乳腺癌模型中增强了肿瘤细胞的死亡，抑制了肿瘤生长，延长了小鼠的存活时间，并促进了免疫细胞的浸润，显示了通过诱导热变态反应的显著抗癌潜力。

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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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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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