Engineered E. coli Nissle 1917 for delivery of bioactive IL-2 for cancer immunotherapy.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 08 2023
02 08 2023
Historique:
received:
04
01
2023
accepted:
24
07
2023
medline:
4
8
2023
pubmed:
3
8
2023
entrez:
2
8
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37532747
doi: 10.1038/s41598-023-39365-2
pii: 10.1038/s41598-023-39365-2
pmc: PMC10397246
doi:
Substances chimiques
Interleukin-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12506Informations de copyright
© 2023. The Author(s).
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