A protein called NFIL3 has been identified as a key factor in reducing the long-term performance of CAR T cells used in cancer treatment. Researchers showed that disabling this protein allows the engineered cells to remain active longer and fight tumors more effectively in laboratory models.
Scientists from Columbia University and University Hospital Tübingen conducted a screen of around 400 transcription factors. They linked NFIL3 to CAR T-cell exhaustion, where the modified immune cells gradually lose their ability to target cancer. The team used CRISPR/Cas9 gene editing to remove NFIL3 from the cells. In several mouse models, the edited CAR T cells multiplied more effectively, stayed functional for extended periods, and improved tumor control as well as survival rates. Prof. Judith Feucht of University Hospital Tübingen stated that switching off NFIL3 could be a decisive step toward significantly improving the long-term potency of CAR T cells. Co-first author Celina May noted the goal is to extend the therapy's usefulness to solid tumors. Further studies are required before the approach can be evaluated in patients. The results were published in the journal Cancer Discovery.
