summary: Researchers found that a ketogenic diet enhances the efficacy of CAR T cell therapy by increasing tumor control and survival in mice with lymphoma. The key is beta-hydroxybutyrate (BHB), a metabolite produced during ketosis that CAR T cells prefer over glucose as an energy source. Laboratory models showed that BHB supplementation caused complete cancer remission in most mice and promoted CAR T cell proliferation.
Translational studies in human samples confirmed that higher BHB levels improve CAR T cell performance. This approach is currently being tested in a phase I clinical trial in lymphoma patients. If successful, this low-toxicity and cost-effective strategy could significantly improve cancer immunotherapy outcomes.
Important facts:
- Ketogenic boost: A ketogenic diet increased tumor control and survival in lymphoma-affected mice by increasing the effectiveness of CAR T cells.
- BHB settings: CAR T cells proliferate using beta-hydroxybutyrate (BHB), a metabolite of ketosis, as a fuel source to outpace glucose.
- Clinical trials: A phase I trial is testing BHB supplementation in lymphoma patients receiving CAR T therapy to validate these findings.
sauce: university of pennsylvania
A simple nutritional supplement may offer a new approach to boosting CAR T cell function, according to a study by researchers at the University of Pennsylvania Perelman School of Medicine and the University of Pennsylvania Abramson Cancer Center.
Although this approach needs to be evaluated in clinical trials, early research (Abstract 4) shared at today’s press conference at the 66th American Society of Hematology (ASH) Annual Meeting and Exhibition shows that it could improve blood testing. suggests the possibility of a cost-effective strategy for CAR T cell function and ability to fight cancer.
CAR T-cell therapy is a personalized treatment approach pioneered at Penn Medicine that reprograms a patient’s own immune cells to kill cancer.
“Thousands of blood cancer patients have been successfully treated with CAR T-cell therapy, but it still doesn’t work for everyone,” said co-first author Dr. said researcher Dr. Xiang Liu.
“We took an unprecedented approach to improve CAR T-cell therapy by targeting T-cells through diet, rather than further genetic engineering.”
Liu co-led the study with Dr. Puneeth Guruprasad, who received his PhD from the University of Pennsylvania and is currently a medical student at the Perelman School of Medicine. The first authors worked under the direction of co-senior author Marco Luera, MD, assistant professor of hematology-oncology, investigator in the Center for Cellular Immunotherapy, and scientific director of Penn Medicine’s Lymphoma Program. and Dr. Maayan Levy, assistant professor of microbiology.
CAR T cells prefer BHB as a fuel source
First, the research team used a diffuse mouse model to show that several different diets, including a ketogenic diet, a high-fiber diet, a high-fat diet, a high-protein diet, a high-cholesterol diet, and a control diet, stimulated CAR T cells. The effect on the ability to fight tumors was tested. – Large B-cell lymphoma. They found that mice fed the ketogenic diet had improved tumor control and survival compared to all other diets.
In a subsequent study, they found that high levels of beta-hydroxybutyrate (BHB), a metabolite produced by the liver in response to a ketogenic diet, was an important mediator of this effect.
The study builds on previous work by Levy’s team, which found that BHB strongly inhibits colorectal tumor growth in laboratory experiments.
“Our theory is that CAR T cells prefer BHB as a fuel source rather than the body’s standard sugars, such as glucose,” Guruprasad said. “In other words, when BHB levels increase in the body, CAR T cells become more capable of eliminating cancer cells.”
Translational research in patient samples and healthy volunteers
Next, the researchers tested the combination of BHB supplements and CAR T-cell therapy in a laboratory model of human cancer (standard diet). The results showed that the cancer completely disappeared in the majority of mice, and CAR T cell proliferation and activation was stimulated.
To see if BHB, which naturally occurs at different levels in our bodies, has similar effects in humans, the team evaluated blood samples from patients who had recently undergone CAR T cell therapy and found that higher We found that BHB levels were associated with better CAR T cells in an expanded number of patients.
They also looked at T cells from healthy volunteers who took BHB supplements and found similar changes in the way normal T cells produce energy after exposure to BHB.
Previous studies in several cancer types have examined the effects of dietary treatments, such as high-fiber diets, on response to cancer immunotherapy, but the mechanism behind the BHB effect in this study was , appears to be caused by metabolic changes in the blood. rather than through the gut microbiome, as is the case with high-fiber diets.
Next steps and potential impact
The theory that BHB supplementation may improve response to CAR T cell therapy is being tested in a Phase I clinical trial at Abramson Cancer Center in Medicine, Pennsylvania.
“We’re talking about interventions that are relatively inexpensive and have a low potential for toxicity,” Levy said.
“If the clinical trial data is positive, it will be interesting to think about how these very simple approaches can be combined with diet and other more traditional approaches to increase anti-cancer efficacy. I’m looking forward to it.”
The clinical trial, led by principal investigator Elise Chung, MD, PhD, assistant professor of hematology-oncology, will soon be used to treat patients with relapsed or refractory large-cell B We plan to begin enrolling patients with cellular lymphoma. their treatment.
“As a physician and scientist, I share patients’ excitement about the possibility of new strategies to better treat cancer. And we’re very excited to see it move into clinical trials,” Luera said. .
“However, we would like to emphasize that this study is still preliminary at this time and we do not intend to recommend any diet or supplement to patients based on this study until we have definitive clinical evidence.” .”
Funding: This research was partially funded by the Penn-CHOP Microbiome Core.
About this brain tumor and diet research news
author: megan lake
sauce: university of pennsylvania
contact: Megan Lake – University of Pennsylvania
image: Image credited to Neuroscience News
Original research: Results of this study will be presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exhibition.
