Description:
Highlight
Reprograms cancer-associated fibroblasts to dismantle tumor barriers and improve immune-cell access to solid tumors.
Innovation
Cancer-associated fibroblasts (CAFs) create a physical and immunosuppressive barrier that limits the effectiveness of CAR-T and other immunotherapies in solid tumors. This technology uses transcription factor-based cellular reprogramming to revert tumor-supporting CAFs into normal fibroblast. By remodeling the tumor microenvironment, the platform has the potential to improve immune-cell infiltration and enhance responses to existing cancer immunotherapies
Advantages
- Addresses a major barrier limiting CAR-T and immune-cell therapies in solid tumors.
- Reprograms multiple tumor-supporting cell types rather than targeting tumor cells alone.
- Compatible with existing immunotherapy approaches, including CAR-T, TCR-T, and checkpoint inhibitors.
- Utilizes transcription factor-based reprogramming to remodel the tumor microenvironment rather than deplete stromal cells.
- Potential platform technology applicable across multiple solid tumor types.
Stage of Development
- Tested in vitro with human prostate cancer-associated fibroblast (CAF) models to demonstrate reprogramming toward normal fibroblast phenotypes.
- Tested in vitro with human prostate cancer (PC-3) tumor spheroid models to evaluate tumor-stroma interactions within the tumor microenvironment.
- Demonstrated preliminary transcriptional, protein-expression, and metabolic evidence of CAF-to-normal fibroblast reversion using Vitamin D Receptor (VDR) reprogramming as well as p53 and PPARγ reprogramming.
- Ongoing development of macrophage reprogramming, microfluidic tumor microenvironment models, and in vivo mRNA-based delivery approaches.
Publications
https://www.biorxiv.org/content/10.64898/2026.04.15.718753v1.full