Discovery Broadens Applications for CAR T-Cell Therapy
Chimeric antigen receptor (CAR) T-cell therapy uses a patient’s modified T-cells to target their cancer. This therapy takes advantage of what T-cells do naturally – find and destroy invaders.
While CAR T-cell therapy has been a game-changer, it is not effective at treating all types of cancer. In some cases, the engineered T-cells become exhausted and stop fighting. The therapy is also less effective against solid tumors.
Researchers at Children’s Hospital of Los Angeles are investigating ways to broaden the applications for CAR T-cell therapy in leukemia patients. In preliminary studies, they have found that increasing the activity of a gene found in T-cells makes them stronger and longer-lasting. This gene is called BCL11B.
Chintan Parekh, MD, a physician-scientist in the Cancer and Blood Disease Institute at Children’s Hospital Los Angeles, is leading the study.
“So far, in our experiments, these modified T-cells are working harder,” he says. “They don’t exhaust or die off as easily. They stay in the fight longer. This could eventually translate into more effective therapies for patients with resistant leukemia or solid tumors.”
But the potential applications don’t end there. The researchers also found that this same gene instructs developing immune cells to become T-cells. This means that increasing the gene in developing immune cells could encourage T-cell regrowth in patients.
“In patients who need a bone marrow transplant, for example, the chemotherapy can wipe out a patient’s immune system,” said Dr. Parekh. “New immune cells begin to develop from the donor marrow in a few weeks, but T-cells can take months to regenerate.”
A lack of T-cells leaves patients vulnerable to infections and at a greater risk of their leukemia relapsing. Speeding up the regrowth of T-cells could be life-changing. Dr. Parekh’s preclinical studies have shown that, at least in the laboratory, increasing BCL11B does just this.
Dr. Parekh’s research was supported in part by the Leukemia Research Foundation in 2018. In February 2022, Dr. Parekh received a $2.3M grant from the National Institute of Allergy and Infectious Diseases to further pursue his research.