A ketogenic diet has been found to enhance the effectiveness of CAR T-cell therapy, a revolutionary cancer treatment. Researchers at the University of Pennsylvania studied the effects of different diets on CAR T-cell therapy and discovered that a ketogenic diet improved tumor control and survival rates.
The team tested five diets, including a ketogenic diet, against a control diet in a preclinical mouse model of diffuse large B-cell lymphoma. The results showed that mice fed the ketogenic diet experienced significant improvements in tumor control and survival. The researchers then explored the systemic factors driving this effect and found that β-hydroxybutyrate (BHB), a key metabolite of the ketogenic diet, was responsible.
Studies revealed that BHB acts as an efficient energy source for CAR T-cells, particularly in the tumor microenvironment. It increased oxygen consumption, energy production, and cytokine secretion, which are critical markers of CAR T-cell functionality. Additionally, BHB increased histone acetylation in CAR T-cells by enhancing Acetyl-coenzyme A (acetyl-CoA) availability.
The researchers found that deleting BDH1, the key enzyme involved in BHB metabolism to acetyl-CoA, reduced the functional benefit observed from BHB. This confirmed that BHB enhances CAR-T function through metabolic modulation.
The translational potential of these findings was supported by two studies. One study showed a positive correlation between BHB levels and CAR T-cell expansion in patients undergoing CAR T-cell therapy. Another small-scale interventional study demonstrated that oral BHB supplementation enhanced T-cell respiratory capacity and energy production, suggesting that BHB could improve CAR T-cell performance in clinical settings.
The results demonstrate that a ketogenic diet or BHB supplementation can significantly enhance CAR T-cell therapy. This approach holds promise for improving outcomes in relapsed or refractory cancers and could pave the way for integrating dietary strategies into cancer immunotherapy protocols. A clinical trial is currently underway to evaluate the safety and efficacy of BHB supplementation in patients with non-Hodgkin lymphoma receiving CAR T-cell therapy.
Source: https://www.pharmacytimes.com/view/ketogenic-diet-and–hydroxybutyrate-may-enhance-car-t-cell-therapy-efficacy