Engineered E. coli Nissle 1917 for delivery of bioactive IL-2 for cancer immunotherapy

被引：14
作者：
Tumas, Sarunas [1 ]
Meldgaard, Trine Sundebo [2 ]
Vaaben, Troels Holger [1 ]
Hernandez, Sara Suarez [2 ]
Rasmussen, Annemette Tengstedt [1 ]
Vazquez-Uribe, Ruben [1 ]
Hadrup, Sine Reker [2 ]
Sommer, Morten O. A. [1 ]
机构：
[1] Tech Univ Denmark, Novo Nord Fdn Ctr Biosustainabil, Lyngby, Denmark
[2] Tech Univ Denmark, Dept Hlth Technol, Lyngby, Denmark
来源：
SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期
关键词：
SALMONELLA-TYPHIMURIUM; RECOMBINANT PROTEINS; TUMOR-GROWTH; INTERLEUKIN-2; EXPRESSION; BACTERIA; THERAPY; METASTASES; TOOL;
D O I：
10.1038/s41598-023-39365-2
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：11
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