Studying the Keto Diet's Impact on CAR T-Cells for Large B-Cell Lymphoma

Researchers Shan Liu, PhD, and Puneeth Guruprasad, PhD, from the University of Pennsylvania, led research efforts to identify if certain diets can improve the effectiveness of CAR T-cell therapy for large B-cell lymphoma. Learn insights from their findings below. 

The Keto Diet’s Influence on CAR T-Cells in Mice 

In laboratory studies with mice who had cancerous tumors, researchers compared various diets, including high-fiber, high-protein, Western diet, high-fat, and ketogenic diets. Mice fed a ketogenic diet showed the most promising results in reducing tumor size.  

This improvement was linked to the ketogenic diet's ability to produce higher levels of a ketone called β-hydroxybutyrate (BHB), which serves as an efficient energy source for CAR T-cells. Further experiments revealed that even when mice were on a control diet, supplementing with BHB enhanced CAR T-cell activity.

BHB Supplement Effects on Human CAR T-Cells

When scientists tested BHB on human CAR T-cells in the lab, they observed increased cell expansion and improved mitochondrial function, which supported the immune cells in fighting cancer more effectively. 

Additionally, a retrospective analysis found that higher BHB levels in patients' blood after CAR T-cell infusion correlated with better T-cell expansion, which is key for this therapy to work. Importantly, this effect didn't increase the risk of cytokine release syndrome (a common and serious side effect). 

BHB and CAR-T Clinical Trial for LBCL Patients

To build on these findings, the research team plans to conduct a clinical trial to evaluate the effects of BHB supplementation in large B-cell lymphoma (LBCL) patients receiving one of the commercially available anti-CD19 CAR T-cell therapies such as axi-cel (Yescarta, Kite) or tisa-cel (Kymriah, Novartis). 

The supplementation will begin between the lymphodepletion phase and CAR T-cell infusion. This study will help determine whether BHB can be safely and effectively integrated into a dietary strategy to improve treatment outcomes.

Christopher D'Angelo, MD, from the University of Nebraska Medical Center, shared his insights about the study. Watch his interview below. 

A Word of Caution

While this research is promising, it’s important to note that they are early-stage findings based on limited studies conducted only in mice and laboratory settings. Evaluating BHB as a supplement in combination with CAR T-cell therapy has not yet been tested in humans. What works in laboratory settings may have different effects on humans. 

You should never make significant changes to your diet or start any supplements without first discussing them with your healthcare team. They can review the potential benefits and risks based on your specific situation, including any reactions the supplements may have with your current medications. 

Key Takeaways

It’s exciting to see new research efforts trying to pinpoint how new therapies can be further boosted with diet and supplementation. While early research suggests that a ketogenic diet’s metabolite BHB may enhance the effectiveness of CAR T-cells, these findings are still in the experimental stages.

Clinical trials will provide essential insights into the safety and effectiveness of BHB supplementation in humans receiving CAR T-cell therapy. Speak with your doctor before making significant changes to your diet or starting new supplements. 

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Sources: 

• Ketogenic Diet Enhances CAR T Cell Antitumor Function Via β-Hydroxybutyrate
• Research Shows How Lifestyle Factors and Diet Affect Hematologic Care
• Ketogenic Diet During CAR-T Therapy for DLBCL