Goal of the project
Oxidative stress in the tumor microenvironment (TME) drives T and NK cell exhaustion and limits their ability to fight cancer. Currently, no available platform can both monitor and counteract this stress in real time.
This project aims to establish the RE-FUEL platform (Responsive Engineering for Immune Cell Fitness in Nutrient-Deprived Settings). The platform combines real-time oxidative stress sensing with inducible release of IL-15, enabling both tracking and restoration of immune cell function in hostile tumor environments.
The modular design also provides opportunities for future adaptation to different tumor microenvironments and therapeutic settings.
Status update
We are currently establishing the RE-FUEL platform in engineered T and NK cells and validating the individual circuit components: HyPer7, which functions as a real-time sensor of oxidative stress, and a synthetic ARE promoter that is activated in response to oxidative stress. Once activated, the system triggers release of IL-15, a signaling molecule that supports immune cell survival and function.
Initial studies focus on assessing oxidative stress responses, inducible IL-15 release, and immune cell function under tumor-relevant metabolic stress conditions.
Grant details
- Awardee: Postdoc Karine Flem Karlsen, PhD, Olweus group.
- Title of project: RE-FUEL: Responsive engineering for immune cell fitness in nutrient-deprived settings
- Collaborative groups: Olweus and Malmberg
- Project participant: Postdoc Alenka Djarmila Behsen, PhD, Malmberg group
- PRIMA Synergy Grant (09): 200 000 NOK
What do you think of the grant mechanism?
"Although collaborative ties within PRIMA are strong, the Synergy Grant mechanism gives young researchers the opportunity to establish and examine concrete ideas that may benefit several groups or the whole PRIMA community. Beyond scientific output, the Synergy Grant is formative at a personal level: leading a project from conception to execution across group boundaries has given us the chance to develop leadership experience that is essential for an independent research career", Karine says.