Spatiotemporal control of engineered bacteria to express interferon-γ by focused ultrasound for tumor immunotherapy.
Spatiotemporal control of engineered bacteria to express interferon-γ by focused ultrasound for tumor immunotherapy.
复制标题
聚焦超声时空控制工程菌表达干扰素-γ用于肿瘤免疫治疗。
DOI：
10.1038/s41467-022-31932-x
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发表时间：
2022-08-02
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
基于细菌的肿瘤治疗由于其独特的靶向肿瘤和优先定植于肿瘤核心区域的能力而近年来受到广泛关注。各种治疗基因也被携带到这些工程菌中，以增强其抗肿瘤功效。然而，很难时空控制这些插入基因在肿瘤部位的表达。在这里，我们设计了一种超声响应细菌（URB），它可以以超声可控的方式诱导外源基因的表达。利用超声波在组织穿透方面的优势，设计一种温度驱动的基因开关，可以实现细菌基因表达的声遥控。细胞因子干扰素-γ（IFN-γ）是一种重要的免疫调节分子，在肿瘤免疫治疗中起着重要的作用，用于测试系统。结果表明，聚焦超声短暂热疗可促进IFN-γ基因的表达，提高URB的体内外抗肿瘤效果。我们的研究为细菌介导的肿瘤免疫治疗提供了一种替代策略。最近已经提出了几种方法来工程化细菌用于癌症免疫治疗。在这里，作者设计了一种超声响应细菌，用于在肿瘤部位控制IFNy的释放，促进临床前模型中的抗肿瘤免疫反应。
Bacteria-based tumor therapy has recently attracted wide attentions due to its unique capability in targeting tumors and preferentially colonizing the core area of the tumor. Various therapeutic genes are also harbored into these engineering bacteria to enhance their anti-tumor efficacy. However, it is difficult to spatiotemporally control the expression of these inserted genes in the tumor site. Here, we engineer an ultrasound-responsive bacterium (URB) which can induce the expression of exogenous genes in an ultrasound-controllable manner. Owing to the advantage of ultrasound in tissue penetration, an acoustic remote control of bacterial gene expression can be realized by designing a temperature-actuated genetic switch. Cytokine interferon-γ (IFN-γ), an important immune regulatory molecule that plays a significant role in tumor immunotherapy, is used to test the system. Our results show that brief hyperthermia induced by focused ultrasound promotes the expression of IFN-γ gene, improving anti-tumor efficacy of URB in vitro and in vivo. Our study provides an alternative strategy for bacteria-mediated tumor immunotherapy. Several approaches have been recently proposed to engineer bacteria for cancer immunotherapy. Here the authors design an ultrasound-responsive bacterium for the controlled release of IFNy at the tumor site, promoting anti-tumor immune responses in preclinical models.
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影响因子：
13
作者：
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通讯作者：
Zoon KC
影响因子：
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影响因子：
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