NEW YORK, June 7 — Researchers have identified a master switch that exhausts CAR T cells and shown how disabling it could help the therapy work against solid tumors.
A team at Columbia University and University Hospital Tubingen, led by Michel Sadelain and Judith Feucht, made the discovery, which could potentially help across many cancers, including breast, lung and pancreatic tumors that have resisted current cell therapies. They screened transcription factors, the master regulators of gene activity, and found that one called NFIL3 was a primary driver of T-cell exhaustion. This breakthrough is significant because CAR T-cell therapy has transformed treatment of some blood cancers, but the engineered cells burn out too quickly against solid tumors, which make up the majority of cancers.
Using CRISPR gene editing to delete the gene responsible for NFIL3, the modified CAR T cells stayed active and multiplied for far longer and maintained a sustained anti-tumor assault. In mouse models, including solid tumors, the edited cells delivered stronger tumor control and extended survival compared with standard CAR T cells.
The approach targets the biology of exhaustion itself rather than a specific tumor type, which is why researchers are hopeful it could have a broad impact.
Because the work was published in Cancer Discovery, it remains early-stage laboratory research that has not yet been tested in patients. People with cancer should consult their doctor about appropriate treatment options, as this research, while promising, is still in its early stages.
The fact that the team was able to identify a master switch that exhausts CAR T cells and show how disabling it could help the therapy work against solid tumors is a significant step forward in the fight against cancer.
Consult your doctor for medical advice.
