New Investigator Grant Awarded to Sneha Ramakrishna

Over the past decade, children with certain types of cancer have been successfully treated with a new therapy called chimeric antigen receptor T cells (CAR T cells). CAR T cells work by teaching the immune system, specifically the T cells, to find and kill cancer cells. However, until recently CAR T cells were unavailable in children with brain tumors. In 2021, Stanford doctors, including myself, opened a clinical trial to use CAR T cells to treat children and young adults with Diffuse Intrinsic Pontine Glioma (DIPG), a universally fatal tumor of the brain. Excitingly, 10 out of 12 subjects infused with these CAR T cells have responded with tumors shrinking and improvement in their symptoms. Unfortunately, not all patients respond to the treatment and we now know that, at least for some patients, the tumor can resist the treatment. My project seeks to learn from our patients to understand why CAR T cells succeeded or failed, with the goal of identifying approaches to improve this treatment for our patients. To do so, I developed a comprehensive platform to collect patient samples throughout CAR T cell treatment. Using these precious patient samples, this proposal will evaluate the features of CAR T cells and other immune populations as they relate to CAR T cell activity and patient response. We will identify predictors or drivers of CAR T cell activity in patients and will also evaluate mechanisms of resistance in patients where the tumor did not respond. By asking questions about the biology in our patients after we give them CAR T cells, we will be able to learn how to improve the treatment, with the ultimate goal to cure this incurable disease.