Researchers are on track to help CAR-T cells – a revolutionary type of cancer immunotherapy – remain effective for longer periods in patients’ bodies, according to two separate reports published on Wednesday in Nature.
Manufacturing of CAR-T cells involves removing a patient’s own T cells, a key component of the immune system, genetically altering them, and re-infusing them. The reprogrammed T cells can recognize and kill cancer cells. “But they tend to get exhausted if the fight goes on for a long time,” a commentary published with the studies explains.
The longer the CAR-T cells survive in the patient’s body, the more effectively they respond to cancer, but fewer than 50% of patients who receive CAR-T cell therapy remain cured after a year, Evan Weber of University of Pennsylvania Perelman School of Medicine in Philadelphia and colleagues noted in one of the reports.
In laboratory experiments, they found that a protein called FOXO1 improves the function and survival of CAR T cells.
In the absence of FOXO1, human CAR-T cells lose their ability to recognize and attack cancer cells in animals, they found. Engineering the CAR-T cells to have higher FOXO1 levels turned on memory genes and enhanced the cells’ ability to persist and fight cancer in animal models.
The researchers also saw evidence that FOXO1 activity in patient samples correlates with long-term disease control.
A separate team from Australia reported similar findings.
“These findings may help improve the design of CAR-T cell therapies and potentially benefit a wider range of patients,” Weber said in a statement.
This newsletter was edited by Bill Berkrot; additional reporting by Shawana Alleyne-Morris.
