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短芽孢杆菌在细菌性癌症治疗中的潜在作用：肿瘤内提供肿瘤坏死因子-α和抗癌作用

Potential usefulness of Brevibacillus for bacterial cancer therapy: intratumoral provision of tumor necrosis factor-α and anticancer effects

原文发布日期：2017-12-18

英文摘要：

摘要翻译：

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短芽孢杆菌在细菌性癌症治疗中的潜在作用：肿瘤内提供肿瘤坏死因子-α和抗癌作用

Potential usefulness of Brevibacillus for bacterial cancer therapy: intratumoral provision of tumor necrosis factor-α and anticancer effects

原文发布日期：2017-12-18

英文摘要：

Bacterial cancer therapy, wherein bacteria are used as a gene expression system for the exogenous protein of interest in the body, has started becoming a focus area of research; therefore, studying potential bacterial species for use is extremely important. Here, we investigated the use of Brevibacillus choshinensis as an effective and safe provider of anticancer proteins in the body, using a transformant expressing murine tumor necrosis factor-α (mTNF-α). The transformant sustainably provided mTNF-α in tumors in mice for a few hours post-injection. The growth of TNF-α-sensitive tumors was inhibited even by the control transformant, which did not provide mTNF-α; intratumoral mTNF-α provision by Brevibacillus choshinensis had additive effects on tumor growth inhibition. In contrast, intratumorally injected recombinant mTNF-α did not inhibit tumor growth because of rapid elimination from the tumor. Blood biochemical and histochemical analyses showed that intravenous injection of the transformant that did not provide mTNF-α did not lead to tissue injury and dysfunction or infiltration of inflammatory cells over 1 week. Considering the findings, this approach is expected to have a high degree of usability as a delivery system for protein pharmaceuticals, especially from the viewpoints of loading capacity and cost effectiveness.

摘要翻译：

细菌抗癌疗法——即利用细菌作为体内外源目的蛋白的基因表达系统——正逐渐成为研究焦点领域，因此筛选具有应用潜力的菌种显得尤为重要。本研究探讨了使用短小芽孢杆菌（Brevibacillus choshinensis）作为体内高效安全递送抗癌蛋白的载体，通过采用表达鼠源肿瘤坏死因子-α（mTNF-α）的转化子进行实验。该转化子在注射后数小时内能持续向小鼠肿瘤组织提供mTNF-α。研究显示，即便是不表达mTNF-α的对照转化子也能抑制TNF-α敏感型肿瘤的生长；而短小芽孢杆菌瘤内提供mTNF-α的能力对肿瘤生长抑制产生了叠加效应。相比之下，瘤内注射的重组mTNF-α因从肿瘤组织中快速清除而未显现抑瘤效果。血液生化及组织化学分析表明，静脉注射不表达mTNF-α的转化子一周后，未引发组织损伤与功能障碍，也未引起炎症细胞浸润。综合研究结果，该方法在载药能力与成本效益方面展现出显著优势，有望成为蛋白质药物递送系统的高实用性解决方案。