TY - JOUR
T1 - Engineered E. coli Nissle 1917 for delivery of bioactive IL-2 for cancer immunotherapy
AU - Tumas, Sarunas
AU - Meldgaard, Trine Sundebo
AU - Vaaben, Troels Holger
AU - Suarez Hernandez, Sara
AU - Rasmussen, Annemette Tengstedt
AU - Vazquez-Uribe, Ruben
AU - Hadrup, Sine Reker
AU - Sommer, Morten O.A.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-023-39365-2
DO - 10.1038/s41598-023-39365-2
M3 - Journal article
C2 - 37532747
AN - SCOPUS:85166404229
SN - 2045-2322
VL - 13
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12506
ER -
