University of Pennsylvania researchers uncover dietary boost for CAR T Cell Therapy

Simple Diet Change Could Revolutionize Cancer Treatment: A groundbreaking study from researchers at the Perelman School of Medicine at the University of Pennsylvania and Penn Medicine’s Abramson Cancer Center has revealed a simple yet potentially transformative strategy to enhance CAR T cell therapy—a revolutionary cancer treatment. The study suggests that the immune system’s cancer-fighting abilities could get a significant boost by harnessing the power of a dietary supplement.

The findings were presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, offering a fresh perspective on the future of cancer treatment. While still in its early stages and requiring further clinical testing, the approach could pave the way for a more cost-effective, accessible enhancement to this cutting-edge therapy.

Also Read: Stanford University researcher finds that young people are at growing risk from extreme heat

What Is CAR T Cell Therapy?

CAR T cell therapy is an immunotherapy that reprograms a patient’s T cells—critical components of the immune system—to recognize and destroy cancer cells. This personalized treatment has been a game-changer for patients with certain blood cancers. However, it doesn’t work for everyone, and researchers have been exploring ways to improve its effectiveness.

“Thousands of patients with blood cancers have been successfully treated with CAR T cell therapy, but it still doesn’t work for everyone,” explained Shan Liu, PhD, a postdoctoral fellow and co-lead author of the study. “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 Key to Boosting CAR T Cells: A Ketogenic Diet

The researchers examined various diets, including ketogenic, high-fiber, high-fat, high-protein, high-cholesterol, and control diets, using a mouse model of diffuse large B-cell lymphoma—a type of blood cancer. They discovered that mice on a ketogenic diet showed significantly better tumour control and survival rates than those on other diets.

The secret ingredient? Beta-hydroxybutyrate (BHB) is a molecule produced by the liver during ketosis—a metabolic state triggered by a ketogenic diet.

“Our theory is that CAR T cells prefer BHB as a fuel source rather than standard sugars like glucose,” said Puneeth Guruprasad, PhD, another co-lead author. “Increasing BHB levels gives the CAR T cells more power to take out cancer cells.”

Building on Previous Research

The findings build on earlier work from the Maayan Levy, PhD team, who co-led the study. Her research showed that BHB suppressed the growth of colorectal tumours in lab experiments.

“Our work suggests that CAR T cells can thrive on BHB, which appears to supercharge their cancer-fighting capabilities,” Levy said.

Translational Studies and Human Impact

The researchers didn’t stop at mouse models. They tested the effect of a BHB supplement on CAR T cell therapy in laboratory models of human cancer. Even with a standard diet, the BHB supplementation led to remarkable results—complete tumour eradication in most cases and significantly higher CAR T cell activation and expansion.

The team examined blood samples from CAR T cell therapy patients to assess its potential in humans. They found that patients with higher natural levels of BHB had better CAR T cell expansion, a critical factor for the therapy’s success. Additionally, T cells from healthy volunteers who took a BHB supplement demonstrated similar metabolic changes, further supporting the hypothesis.

Beyond the Gut

Dietary interventions have long been studied for their impact on cancer treatment. High-fiber diets, for instance, are thought to influence cancer immunotherapy through the gut microbiome. However, the BHB effect works differently.

“This mechanism seems to be linked to metabolic changes in the blood rather than the gut microbiome,” Levy noted.

A New Phase in Cancer Treatment

Excitement is growing as the theory moves from the lab to clinical trials. A Phase I trial at Penn Medicine’s Abramson Cancer Center will soon enrol patients with relapsed or refractory large B-cell lymphoma who are undergoing CAR T cell therapy. The trial, led by principal investigator Elise Chong, MD, will explore whether BHB supplementation can enhance the therapy’s efficacy.

“We’re talking about an intervention that is relatively cheap and has low toxicity potential,” Levy said. “If the clinical trial data pans out, I’m excited to think about how a fairly simple approach like this could be combined with dietary interventions or more traditional approaches to enhance the anti-cancer effect.”

Cautious Optimism

While the study’s results are promising, the researchers emphasize that it’s too early to make dietary or supplement recommendations to patients.

“As a physician and scientist, I share my patients’ excitement for potential new strategies to treat their cancer better,” said Marco Ruella, MD, co-senior author and assistant professor of Hematology-Oncology. “But we want to emphasize that this research is still preliminary. We need definitive clinical evidence before making any recommendations.”

The Road Ahead

If successful, this simple dietary intervention could profoundly impact the field of cancer treatment. For patients, it represents a potentially low-cost, low-risk addition to their therapeutic arsenal. It opens new doors for researchers to explore how metabolism influences immune function.

The study’s implications extend beyond CAR T cell therapy, suggesting a broader role for diet and metabolism in shaping immune responses. With clinical trials on the horizon, the medical community eagerly awaits the next chapter in this exciting story.

Also Read: Harvard University researchers developed an AI system to protect high-risk communities from HIV

As Guruprasad aptly summarized, “This is just the beginning. We hope our work could lead to a future where simple, accessible interventions make advanced cancer therapies even more effective.”

The Penn-CHOP Microbiome Core partly funded this study, and the team’s pioneering work highlights the intersection of diet, metabolism, and cutting-edge immunotherapy. Follow Education Post News for breaking news and global updates.