A simple dietary supplement in ketogenic diet can boost ‘CAR T’ cell function — a personalised treatment that reprogrammes patients’ own immune cells to kill cancer, according to a new study.

While the approach needs to be assessed in clinical trials, the early research, hints at a potentially cost-effective strategy to improve CAR T cell function and cancer-fighting abilities, according to a study from researchers in the Perelman School of Medicine at the University of Pennsylvania and Penn Medicine’s Abramson Cancer Center in the US.

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“Thousands of patients with blood cancers have been successfully treated with CAR T cell therapy, but it still doesn’t work for everyone,” said co-lead author Shan Liu, a postdoctoral fellow.

Liu co-led the study with Puneeth Guruprasad, a medical student in the Perelman School of Medicine.

The research team tested the effect of several different diets, including ketogenic, high-fibre, high-fat, high-protein, high cholesterol, and a control diet, on CAR T cell’s tumour-fighting capabilities using a mouse model of diffuse-large B-cell lymphoma.

They found improved tumour 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.

“Our theory is that CAR T cells prefer BHB as a fuel source rather than standard sugars in our body, such as glucose,” Guruprasad said. “So, increasing the levels of BHB in the body gives the CAR T cells more power to take out the cancer cells.”

The theory that BHB supplementation could 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 is relatively cheap and has low toxicity potential,” said Maayan Levy, PhD, an assistant professor of Microbiology.

“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 other, more traditional approaches, to enhance the anti-cancer effect,” Levy added.