Although the approach needs to be evaluated in clinical trials, preliminary research points to a potentially cost-effective strategy to improve CAR T cell function and cancer-fighting abilities, Perelman of the University According to a study by researchers at the School of Medicine. of the Abramson Cancer Center of Pennsylvania and Penn Medicine in the US.
“Thousands of blood cancer patients have been successfully treated with CAR T cell therapy, but it still doesn’t work for everyone,” said co-lead author Sean Liu, a postdoctoral fellow.
Liu co-led the study with Puneeth Guru Prasad, a medical student at the Perelman School of Medicine.
The research team tested the effects of several different diets, including a ketogenic, high-fiber, high-fat, high-protein, high-cholesterol, and control diet, on the tumor-fighting abilities of CAR T cells using a mouse model. B-cell lymphoma.
They found better tumor control and survival in mice receiving the ketogenic diet compared to all other diets.
In a later study, they found higher levels of beta-hydroxybutyrate (BHB), a metabolite produced by the liver in response to a ketogenic diet, was an important mediator of this effect.
“Our theory is that CAR T cells prefer BHB as a fuel source in our body rather than standard sugars, such as glucose,” said Guruprasad. “So, increasing BHB levels in the body gives CAR T cells more power to knock out cancer cells.”
The idea that BHB supplementation may improve response to CAR T cell therapy is being tested in a Phase I clinical trial at Penn Medicine’s Abramson Cancer Center.
“We’re talking about an intervention that’s relatively inexpensive and has a low potential for toxicity,” said Mayan Levy, PhD, assistant professor of microbiology.
Levy added, “If the clinical trial data pans out, I’m excited to think about how a simple approach like this could be combined with dietary interventions or other traditional approaches to treat cancer. The adverse effect can be amplified.”