Enhancing GD2-CAR NKT anti-tumor efficacy against neuroblastoma by targeting BLIMP1

Dr. Gengwen Tian, M.D., Ph.D. – Baylor College of Medicine, Houston TX

My research focuses on training a special type of immune cell called a natural killer T cell (NKT) to recognize and kill neuroblastoma (NB) tumor cells without causing the toxic side effects associated with traditional chemotherapy. NB is the most common and hardest to treat pediatric solid tumor outside of the brain. We initiated the first trial in humans to treat patients with their own NKT cells engineered to express a chimeric antigen receptor (CAR) that targets NB cells and spares healthy cells. While the therapy was safe and generated some clinical responses, most did not last and the NKT cells did not persist long-term in the blood. Findings from recent research in my group showed that a protein called BLIMP1 impacts how long CAR-NKTs persist in the body and that when BLIMP1 expression is lower, CAR-NKTs tend to persist longer. However, we also found that when we completely remove BLIMP1 expression through genetic “knock-out,” CAR-NKTs become less effective at killing NB cells. Thus, my current research aims to use two unique strategies with the goal of improving CAR-NKT persistence without compromising their ability to kill NB cells.