Researchers from Columbia University and University Hospital Tübingen have identified a protein called NFIL3 that plays a key role in weakening CAR-T cells. The findings, published in the journal Cancer Discovery, suggest that disabling this protein could help CAR-T cells maintain their anti-cancer activity for a longer period.

CAR-T therapy is one of the most advanced forms of cancer immunotherapy. In this approach, a patient’s immune cells are genetically engineered to recognize and destroy cancer cells. While the therapy has shown remarkable success in certain blood cancers, its effectiveness against solid tumors has remained limited.

By analyzing approximately 400 transcription factors, the researchers identified NFIL3 as a major driver of CAR-T cell exhaustion—a process that gradually reduces the cells’ ability to fight cancer. Using the gene-editing technology CRISPR/Cas9, the team disabled the gene responsible for producing NFIL3 and found that CAR-T cells remained more active, proliferated more efficiently, and exhibited stronger anti-tumor effects.

Experiments in animal models also demonstrated that the removal of NFIL3 resulted in better tumor control and improved survival. The researchers believe that this discovery could pave the way for more effective treatments of solid tumors and expand the use of CAR-T therapy to a broader range of cancers.

However, the scientists emphasized that further studies are needed to evaluate the safety and effectiveness of this approach before it can be tested in patients.

https://www.sciencedaily.com/releases/2026/06/260602021641.htm