Engineered E. coli Nissle 1917 for delivery of bioactive IL‑2 for cancer immunotherapy
Engineered E. coli Nissle 1917 for delivery of bioactive IL‑2 for cancer immunotherapy
“Cancer patients with bacterial infections showed significant tumor regression.” What seems to be an extraordinary statement is in fact an elementary principle of bacterial-based immunotherapy. The 18th century sought crude attempts at re-emulating such an outcome, by developing bacterial-based therapies, albeit inconclusively.
However, recent advancements of synthetic biology have pushed the field of Advanced Microbial Therapeutics to exploit the power of tumor-homing bacteria.
On account of Cureline Baltic’s director of preclinical operations, Dr Sarunas Tumas, “The idea of the paper is to challenge the notion that for bacterial cancer therapy you can just express whatever protein or cytokine as high as possible and think that it is active in the tumor microenvironment.”
Truly enough, Dr Tumas’ team, demonstrated how a fine-tuned optimization is needed for selecting the best export signal, solubility enhancer and expression strength to obtain a secreted protein that is active.
Abstract
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.Find the full article Published in Nature!
