Recent groundbreaking research suggests that adopting a ketogenic diet might significantly boost the effectiveness of chimeric antigen receptor (CAR) T-cell therapy, a transformative treatment for various cancers. This cutting-edge study, presented by Dr. Shan Liu during the 2024 American Society of Hematology (ASH) Annual Meeting, highlights β-hydroxybutyrate (BHB)—a compound produced when the body enters a ketogenic state—as a key factor enhancing CAR T-cell function.

"Our research has unveiled that a ketogenic diet can markedly amplify CAR T-cell efficacy. BHB, one of the notable metabolites generated through this diet, plays a pivotal role in mediating this positive effect," stated Dr. Liu, a postdoctoral researcher at the prestigious Perelman School of Medicine at the University of Pennsylvania. Notably, two-thirds of patients receiving CAR T therapy report limited responses or experience relapse, making dietary modifications a potentially attractive adjunct to this already powerful treatment.

This remarkable study stands out as the first to investigate how specific dietary changes can influence the antitumor capabilities of CAR T-cell immunotherapy.

BHB's Role and the Study's Insights

In their innovative experiments, researchers evaluated several dietary regimens—including high-fiber, high-fat, high-protein, and ketogenic diets—in mice diagnosed with B-cell lymphoma. Astonishingly, the mice on a ketogenic diet exhibited superior tumor management and overall survival rates post-CAR T-cell therapy. Through further investigation, it was determined that BHB was the critical metabolite that increased following the ketogenic diet. Mice on a standard diet supplemented with BHB showed enhanced CAR T-cell proliferation and more effective tumor control compared to those without such supplementation.

Moreover, BHB appears to optimize CAR T-cell function by serving as a more efficient energy source than glucose, typically utilized by most cells. In tests using T cells harvested from lymphoma patients for CAR T-cell production, BHB supplementation in the culture medium significantly improved T-cell growth and mitochondrial function. Retrospective blood analysis of 17 patients undergoing CAR T therapy for large B-cell lymphoma revealed that higher BHB levels correlated with more substantial CAR T-cell expansion.

To further investigate the implications of BHB intake, researchers engaged healthy volunteers to monitor T-cell performance before and after BHB supplementation. The analysis indicated a remarkable enhancement in mitochondrial function of T-cells, lending credence to the hypothesis that BHB boosts T-cell activity by refining energy processing.

Caution and Future Directions

Despite the promising lab and animal study results, researchers urge caution, emphasizing that clinical trials involving actual CAR T-cell therapy patients are pivotal for validating these findings. "At this stage, we do not recommend the adoption of a ketogenic diet or the use of BHB supplements during CAR T therapy," cautioned Dr. Liu. However, the research team announced plans to initiate a clinical trial soon, focusing on cancer patients undergoing CAR T-cell therapy to explore the effects of BHB supplementation further.

In conclusion, while the prospect of a ketogenic diet enhancing CAR T-cell therapy is tantalizing, further research will be essential in determining its clinical applicability and safety. Stay tuned for more updates as this exciting field of study unfolds!