The composition of donor cord blood may play a critical role in the success of chimeric antigen receptor (CAR) natural killer (NK) cell therapies. A small population of immature NK cells present in donor cord blood can undermine the activity of CAR NK cell therapy by redirecting potent immune cells away from tumors and causing them to attack one another. The study, led by first and co-corresponding author Ye Ethan Li, M.D., Ph.D., identifies a previously unrecognized mechanism of CAR NK cell dysfunction and offers a practical strategy to improve the potency and consistency of future off-the-shelf NK cell therapies.
“Our findings show that a relatively small population of immature NK cells can have a disproportionately harmful effect on the entire therapeutic product,” said principal investigator Katy Rezvani, M.D., Ph.D., vice president and head of the Institute for Cell Therapy Discovery & Innovation, and professor of Stem Cell Transplantation and Cellular Therapy. “Importantly, this is a problem we can potentially address with a straightforward manufacturing strategy by removing these cells before therapy production.”


