Chimeric antigen receptor (CAR) T cells have successfully treated children and adults with leukemia, including patients who relapse. But CAR T cells have been less successful against solid tumors.
Scientists thought too many CAR T cells become a quick-acting type of T cell called effector cells. Too few become long-lasting memory cells.
St. Jude scientists tested a way to change that and improve CAR T-cell therapy. They found that a protein complex called cBAF directs T cells to become effector cells. Inhibiting cBAF in CAR T cells slowed solid tumor growth in a preclinical mouse model. The treated CAR T cells also lived longer and in higher numbers.
“We showed that inhibitors of cBAF may help generate superior CAR T cells,” said Doug Green, PhD, St. Jude Department of Immunology chair.
Hongbo Chi, PhD, St. Jude Immunology, added, “Our work also showed that by better understanding basic immunobiology and T-cell function, we can develop better therapeutics for cancer and other diseases.”
The results appeared in Nature.