Leo Wang, MD PhD leads a research laboratory at City of Hope focused on harnessing the immune system to fight cancer in children. Work there uses cellular engineering to reprogram the body’s own immune cells to kill tumor cells and to teach reengineered cells to adapt to tumors as they change and evolve to try to escape from therapy. Dr. Wang also leads clinical trials using these living medicines to treat children with brain tumors and other forms of deadly cancer and uses the information learned from these trials to improve the design and implementation of next-generation therapies.

The Pediatric Cancer Research Foundation has funded Dr Wang’s research for four years. Our earliest support enabled Dr Wang and his colleagues to start treating pediatric brain tumor patients with CAR T cell therapy, an innovative immune therapy that uses genetically modified immune cells to defeat cancer. The trial opened in October 2020 during Covid and successfully convinced the California Institute of Regenerative Medicine to fund the trial in April 2021. That support enabled the trial to expand to Children’s Hospital of Los Angeles and to gain real momentum in its efforts to improve CAR T therapy for pediatric brain tumor patients. Working in collaboration with other thought leaders in the field, Dr Wang has been able to examine why CAR T cell therapy works – and doesn’t work – and to use that information to build better CAR T cells. Additionally, his laboratory is working to better understand the specific signals CAR T cells receive when they encounter tumor cells and how to amplify those signals to make better and more robust antitumor immune responses.

Research is predicated on the fact that T recognize viruses, cancer cells and other invaders through their T cell receptors. Normally, each T cell expresses a unique T cell receptor, and our bodies generate hundreds of millions of different T cells. In the current clinical trial, Dr. Wang’s team has found that CAR T cell therapy causes other T cells to expand over time. These expanded T cells are not CAR T cells, and because they are expanded (meaning they all came from one original cell) they all express the same T cell receptor. They are also activated, meaning they are primed to kill. Dr. Wang’s team is working to determine whether these expanded, activated T cells recognize cancer cells or not – and if they do, how to get them to tumor cells more effectively. If they do not, Dr. Wang’s team will investigate how to retarget them to attack tumor cells.