Studies find BHB supplement improves CAR-T cell function

A simple dietary supplement may provide a new approach to boost CAR-T cell function, according to a studies from researchers in the Perelman School of Medicine at the University of Pennsylvania and Penn Medicine’s Abramson Cancer Center.

Early findings, shared last month at the American Society of Hematology Annual Meeting, suggest a simple and scalable strategy to enhance CAR-T cell therapy through diet. Using a mouse model of diffuse-large B-cell lymphoma, researchers saw improved tumor control and survival in mice with that received a ketogenic diet compared to all other diets. In subsequent studies, they found higher levels of beta-hydroxybutyrate (BHB), a metabolite produced by the liver in response to a ketogenic diet, was a key mediator of this effect.

The research team tested a BHB supplement combined with CAR-T cell therapy in lab models of human cancer and the results showed complete obliteration of the cancer in the vast majority of mice and resulted in higher CAR-T cell expansion and activation. The team also assessed blood samples from patients who had recently received CAR-T cell therapy and found that greater BHB levels were associated with better CAR-T cell expansion in patients

The theory that BHB supplementation could improve response to CAR-T cell therapy is being tested in a phase 1 clinical trial at Penn Medicine’s Abramson Cancer Center.