Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.
Sci Rep. 2023 Aug 2;13(1):12506. doi: 10.1038/s41598-023-39365-2.
In this study we performed a step-wise optimization of biologically active IL-2 for delivery using E. coli Nissle 1917. Engineering of the strain was coupled with an in vitro cell assay to measure the biological activity of microbially produced IL-2 (mi-IL2). Next, we assessed the immune modulatory potential of mi-IL2 using a 3D tumor spheroid model demonstrating a strong effect on immune cell activation. Finally, we evaluated the anticancer properties of the engineered strain in a murine CT26 tumor model. The engineered strain was injected intravenously and selectively colonized tumors. The treatment was well-tolerated, and tumors of treated mice showed a modest reduction in tumor growth rate, as well as significantly elevated levels of IL-2 in the tumor. This work demonstrates a workflow for researchers interested in engineering E. coli Nissle for a new class of microbial therapy against cancer.
在这项研究中，我们使用大肠杆菌 Nissle 1917 对具有生物活性的白细胞介素 2（IL-2）进行了逐步优化，以实现其传递。该菌株的工程改造与体外细胞测定相结合，以测量微生物产生的白细胞介素 2（mi-IL2）的生物活性。接下来，我们使用 3D 肿瘤球体模型评估了 mi-IL2 的免疫调节潜力，结果表明其对免疫细胞激活有很强的作用。最后，我们在小鼠 CT26 肿瘤模型中评估了工程化菌株的抗癌特性。该工程化菌株被静脉内注射并选择性地定植于肿瘤中。治疗耐受性良好，并且接受治疗的小鼠的肿瘤生长速度略有降低，肿瘤中的 IL-2 水平显著升高。这项工作展示了一种工作流程，可供对为癌症开发新一类微生物疗法而对大肠杆菌 Nissle 进行工程改造感兴趣的研究人员使用。
