Both-In-One Hybrid Bacteria Suppress the Tumor Metastasis and Relapse via Tandem-Amplifying Reactive Oxygen Species-Immunity Responses,Advanced Healthcare Materials

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Both-In-One Hybrid Bacteria Suppress the Tumor Metastasis and Relapse via Tandem-Amplifying Reactive Oxygen Species-Immunity Responses
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2021-09-20 , DOI: 10.1002/adhm.202100950
Mengchi Sun ₁ , Hao Ye ₁ , Qinghua Shi ₂ , Jun Xie ₂ , Xiang Yu ₃ , Hao Ling ₁ , Song You ₂ , Zhonggui He ₁ , Bin Qin ₁ , Jin Sun ₁

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Bacterial therapy, which targets the tumor site and aims at exerting an antitumor immune response, has displayed a great potential against malignant tumors. However, failure of the phase I clinical trial of Salmonella strain VNP20009 alone demonstrates that bacterial treatment alone can unsatisfy the requirements of high efficiency and biosafety. Herein, a strategy of both-in-one hybrid bacteria is proposed, wherein the chemotherapeutic drug doxorubicin (DOX) is integrated onto the surface of glucose dehydrogenase (GDH)-overexpressed non-pathogenic Escherichia coli (E. coli) strain, to potentiate the antitumor efficacy. Nicotinamide adenine dinucleotide phosphate (NADPH), which is produced by GDH from E. coli, promotes the generation of toxic reactive oxygen species (ROS) within the tumor, and ROS is then catalyzed by the DOX-activated NADPH oxidases. Importantly, the hybrid bacteria enhance stimulated systemic antitumor immune responses, thereby leading to effective tumor eradication. When this strategy is applied in four different tumor models, the hybrid bacteria significantly inhibited tumor metastasis, postsurgical regrowth, and primary/distal tumor relapse. The both-in-one ROS-immunity-boosted hybrid bacteria strategy provides knowledge for the rational design of bacteria-based synergistic cancer therapy.

中文翻译：

合二为一的混合细菌通过串联放大活性氧物种-免疫反应抑制肿瘤转移和复发

以肿瘤部位为靶点，以发挥抗肿瘤免疫反应为目的的细菌疗法，在对抗恶性肿瘤方面显示出巨大的潜力。然而，单独对沙门氏菌菌株 VNP20009 进行I 期临床试验的失败表明，单独的细菌处理不能满足高效和生物安全的要求。在此，提出了一种双合一杂种细菌的策略，其中化学治疗药物阿霉素 (DOX) 被整合到葡萄糖脱氢酶 (GDH) 过表达的非致病性大肠杆菌( E.coli ) 菌株的表面，以增强抗肿瘤功效。烟酰胺腺嘌呤二核苷酸磷酸 (NADPH)，由大肠杆菌中的 GDH 产生, 促进肿瘤内有毒活性氧 (ROS) 的产生，然后 ROS 被 DOX 激活的 NADPH 氧化酶催化。重要的是，杂交细菌增强了受刺激的全身抗肿瘤免疫反应，从而有效地根除肿瘤。当将该策略应用于四种不同的肿瘤模型时，杂交细菌显着抑制了肿瘤转移、术后再生和原发/远端肿瘤复发。双合一 ROS 免疫增强杂交细菌策略为基于细菌的协同癌症治疗的合理设计提供了知识。

更新日期：2021-11-04

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