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Researchers at the University of Pennsylvania explore how a ketogenic diet-based supplement could enhance the effectiveness of CAR T cell therapy for cancer patients
A promising new approach to boosting the effectiveness of CAR T cell therapy—an innovative treatment for cancer—has been uncovered by researchers at the Perelman School of Medicine and the Abramson Cancer Center at the University of Pennsylvania. Recent findings, presented at the 66th American Society of Hematology (ASH) Annual Meeting, suggest that a simple dietary supplement could significantly enhance CAR T cell functionality and improve cancer-fighting capabilities.
CAR T cell therapy, developed at Penn Medicine, is a groundbreaking treatment that reprograms a patient’s immune cells to target and destroy cancer cells. While the therapy has shown success in treating many blood cancers, it remains ineffective for some patients, leaving researchers searching for ways to increase its success rate.
Dr. Shan Liu, a postdoctoral fellow and co-lead author of the study, explained the team’s novel approach: “We took an outside-the-box approach to improve CAR T cell therapy by targeting T cells through diet rather than further genetic engineering.”
The research team, led by Liu and Puneeth Guruprasad, PhD, explored how diet could impact CAR T cell therapy. They focused on beta-hydroxybutyrate (BHB), a metabolite produced during a ketogenic diet, hypothesizing that this compound could act as a preferred fuel source for CAR T cells, enhancing their ability to fight cancer. Their initial laboratory studies on mice with diffuse-large B-cell lymphoma revealed that a ketogenic diet—high in fats and low in carbohydrates—improved tumor control and survival compared to other diets. The team discovered that the key mediator of this effect was BHB.
“We believe that CAR T cells prefer BHB as a fuel source rather than glucose, which is the standard fuel for many cells in the body,” said Guruprasad. “Increasing BHB levels could give CAR T cells the energy boost they need to effectively target and destroy cancer cells.”
The researchers then tested a BHB supplement in combination with CAR T cell therapy in laboratory models of human cancer. The results were promising, showing complete tumor eradication in most of the treated mice and increased expansion and activation of the CAR T cells. Further analysis of blood samples from patients who had recently undergone CAR T cell therapy revealed that higher BHB levels were linked to better CAR T cell expansion. Healthy volunteers who took a BHB supplement also showed increased activation in their T cells.
The next step for this research is a Phase I clinical trial, led by Dr. Elise Chong, at the Abramson Cancer Center. This trial will focus on patients with relapsed or refractory large B-cell lymphoma who are receiving commercially available anti-CD19 CAR T cell therapy.
The potential of this dietary supplement is exciting, as it offers a low-cost, low-toxicity option to potentially improve cancer treatment outcomes. “If the clinical trial data pans out, I’m excited to think about how this simple approach could be combined with other treatments to enhance the anti-cancer effect,” said Dr. Maayan Levy, co-senior author of the study.
While the results are promising, the researchers emphasize that the study is still in its early stages. Dr. Marco Ruella, co-senior author of the study, cautioned, “At this point, we’re not making any dietary or supplement recommendations to patients based on this study until we have definitive clinical evidence.”
The research, partly funded by the Penn-CHOP Microbiome Core, marks a significant step toward improving CAR T cell therapy and could potentially transform the way cancer is treated in the future.
Meeting: 66th American Society of Hematology (ASH) Annual Meeting and Exposition
