A simple dietary supplement may provide a new approach to boost CAR T cell function, according to a study from researchers in Penn’s Perelman School of Medicine (PSOM) and Penn Medicine’s Abramson Cancer Center. While the approach needs to be assessed in clinical trials, the early research, shared in a press briefing on Dec. 7 at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 4), hints at a potentially cost-effective strategy to improve CAR T cell function and cancer-fighting abilities.
CAR T cell therapy is a personalized treatment approach, pioneered at Penn Medicine, that reprograms patients’ own immune cells to kill their cancer.
“Thousands of patients with blood cancers have been successfully treated with CAR T cell therapy, but it still doesn’t work for everyone,” says co-lead author Shan Liu, a postdoctoral fellow who presented the study at ASH. “We took an outside-the-box approach to improve CAR T cell therapy, by targeting T cells through diet rather than further genetic engineering.”
Liu co-led the study with Puneeth Guruprasad, who earned his Ph.D. at Penn and is now a medical student in PSOM. The lead authors worked under the mentorship of co-senior authors Marco Ruella, an assistant professor of Hematology-Oncology, a researcher with the Center for Cellular Immunotherapies and the scientific director of Penn Medicine’s Lymphoma Program; and Maayan Levy, an assistant professor of Microbiology.
First, the research team tested the effect of several different diets, including ketogenic, high-fiber, high-fat, high-protein, high cholesterol, and a control diet, on CAR T cell’s tumor-fighting capabilities using a mouse model of diffuse-large B-cell lymphoma. They found improved tumor control and survival in the mice receiving a ketogenic diet compared to all other diets. In subsequent studies, they found higher levels of beta-hydroxybutyrate (BHB), a metabolite produced by the liver in response to a ketogenic diet, was a key mediator of this effect.
The research builds on previous work from Levy’s team, which found that BHB strongly suppressed the growth of colorectal tumors in lab experiments.
“Our theory is that CAR T cells prefer BHB as a fuel source rather than standard sugars in our body, such as glucose,” Guruprasad says. “So, increasing the levels of BHB in the body gives the CAR T cells more power to take out the cancer cells.”
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