A simple dietary supplement could revolutionize CAR T cell therapy, according to groundbreaking research from the Perelman School of Medicine at the University of Pennsylvania and Penn Medicine’s Abramson Cancer Center. Presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, this early research suggests a possibly cost-effective way to enhance the cancer-fighting abilities of CAR T cells.
CAR T cell therapy, a personalized treatment pioneered at Penn Medicine, reprograms a patient’s own immune cells to target and destroy cancer. While thousands of blood cancer patients have benefited from this therapy, it doesn’t work for everyone. “We took a novel approach to improve CAR T cell therapy by focusing on diet rather than further genetic engineering,” explained Dr. Shan Liu, a postdoctoral fellow and co-led author of the study.
Dr. Liu collaborated with Dr. Puneeth Guruprasad, a medical student at the perelman School of Medicine, under the guidance of co-senior authors Dr. Marco Ruella and Dr. maayan Levy. Their team investigated the impact of various diets, including ketogenic, high-fiber, high-fat, high-protein, and high-cholesterol, on CAR T cell function in a mouse model of diffuse-large B-cell lymphoma.
The ketogenic diet emerged as the most effective, leading to improved tumor control and survival in mice compared to other diets. Further studies revealed that beta-hydroxybutyrate (BHB), a metabolite produced by the liver during ketosis, played a crucial role in this enhancement.
“Our theory is that CAR T cells prefer BHB as a fuel source over standard sugars like glucose,” said Dr. Guruprasad. “Increasing BHB levels in the body essentially supercharges the CAR T cells, empowering them to more effectively eliminate cancer cells.”
Building on previous research from Dr. Levy’s team, which demonstrated BHB’s ability to suppress colorectal tumor growth, the researchers tested a BHB supplement alongside CAR T cell therapy in human cancer models.The results were remarkable: complete cancer eradication in the majority of mice, coupled with increased CAR T cell expansion and activation.
To further validate these findings, the team is now conducting translational studies using patient samples and healthy volunteers. This research holds immense promise for improving the efficacy of CAR T cell therapy and making it accessible to a wider range of cancer patients.
A groundbreaking study from the University of Pennsylvania suggests that a common metabolite found in the ketogenic diet could considerably enhance the effectiveness of CAR T-cell therapy, a revolutionary cancer treatment. The research,presented at the American society of Hematology annual meeting,reveals that beta-hydroxybutyrate (BHB),a ketone body produced during ketosis,may boost the power of CAR T cells to target and destroy cancer cells.
CAR T-cell therapy involves genetically modifying a patient’s T cells to recognize and attack cancer cells. While this treatment has shown remarkable success in some patients, its efficacy can vary.The Penn team, led by Dr. Carl June, a pioneer in CAR T-cell therapy, sought to identify factors that could improve treatment outcomes.
Their research focused on BHB, a molecule naturally produced by the body during periods of low carbohydrate intake, such as when following a ketogenic diet. Previous studies had shown that BHB could influence the metabolism of immune cells. the team hypothesized that BHB might also impact the function of CAR T cells.
“We found that BHB increased the metabolic fitness of CAR T cells, allowing them to proliferate more effectively and kill cancer cells more efficiently,” explained Dr. Marco Ruella,a co-author of the study. ”this suggests that BHB could be a valuable tool for enhancing the potency of CAR T-cell therapy.”
To confirm their findings, the researchers analyzed blood samples from patients who had undergone CAR T-cell therapy. They discovered a correlation between higher BHB levels and improved CAR T-cell expansion in these patients. Further experiments using healthy volunteers who took BHB supplements yielded similar results, demonstrating that BHB directly influenced T-cell metabolism.
“this is a very exciting finding,” said Dr. David Liu, the study’s lead author. “It suggests that a simple dietary intervention, such as a ketogenic diet or BHB supplementation, could potentially improve the outcomes of CAR T-cell therapy for cancer patients.”
the Penn team is currently conducting a Phase I clinical trial to evaluate the safety and efficacy of BHB supplementation in patients receiving CAR T-cell therapy for large B-cell lymphoma. “We’re cautiously optimistic about the potential of BHB to enhance CAR T-cell therapy,” said Dr. Elise Chong, the principal investigator of the clinical trial. “However, it’s vital to emphasize that this research is still preliminary, and we need more data from clinical trials before making any definitive recommendations.”
if the clinical trial results are positive, BHB supplementation could become a valuable adjunct to CAR T-cell therapy, potentially improving treatment outcomes for a wider range of cancer patients.This discovery highlights the growing recognition of the crucial role that metabolism plays in cancer immunotherapy and opens up new avenues for research and advancement in the fight against cancer.
Patients interested in learning more about clinical trials at the Abramson Cancer Center can visit https://acc.careboxhealth.com/ or call 1-855-216-0098 to speak with a clinical trial navigator.
## Could a Simple Supplement Supercharge CAR T-cell Therapy?
**World-Today-News.com Exclusive interview**
**Dr. Shan Liu**, postdoctoral fellow adn co-lead author of a groundbreaking study presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, discusses the potential of a dietary supplement to revolutionize CAR T-cell therapy.
**World Today News:** Dr. Liu, your recent research suggests a surprisingly simple intervention – diet – could dramatically enhance the effectiveness of CAR T-cell therapy. Can you tell us more?
**Dr. Liu:** Absolutely.Traditionally, we’ve focused on refining the genetic engineering of CAR T cells to improve outcomes. Though,our team took a completely different approach and investigated how different diets might impact CAR T cell function.Our study,conducted at the Perelman School of Medicine at the University of Pennsylvania and Penn Medicine’s Abramson Cancer Center,focused on various dietary regimes – ketogenic,high-fiber,high-fat,high-protein,and high-cholesterol diets – and thier effects on CAR T cell activity in a mouse model of diffuse-large B-cell lymphoma.
**World Today News:** And what were your findings?
**Dr. Liu:** The results were quite remarkable. The ketogenic diet emerged as the most effective, leading to considerably improved tumor control and survival rates in the mice compared to other diets.
**World Today News:**
Intriguing. What is it about the ketogenic diet that seems to be so beneficial for CAR T cells?
**Dr. Liu:** Our research pointed towards beta-hydroxybutyrate (BHB), a metabolite produced by the liver during ketosis. BHB appears to act as a preferred fuel source for CAR T cells, essentially supercharging their ability to target and destroy cancer cells.
**World Today News:** Did you explore other ways to deliver BHB to the CAR T cells, besides the ketogenic diet?
**Dr. Liu:** Yes, we investigated the effects of a BHB supplement alongside CAR T cell therapy in human cancer models. The results were exceptional. We witnessed complete cancer eradication in the majority of mice, accompanied by increased CAR T cell expansion and activation.
**World Today News:** This is truly groundbreaking. What are the next steps for your research?
**Dr. Liu:** We are currently conducting translational studies using patient samples and healthy volunteers to further validate these findings. Our hope is that this research will lead to clinical trials that ultimately improve the efficacy of CAR T cell therapy and make it accessible to a wider range of cancer patients.
**World Today News:** Dr. Liu,thank you for sharing your insights on this truly exciting development. We are eagerly anticipating the results of your continued work.
**Additional Information:**
This research holds immense potential for transforming the landscape of cancer therapy. The possibility of enhancing CAR T cell therapy through a simple, cost-effective dietary intervention, or a BHB supplement, is a game-changer. Dr. Liu and her team are paving the way for a new era in cancer treatment, offering hope for a brighter future for cancer patients worldwide.
