Researchers have found that the ketogenic diet can boost the effectiveness of chimeric T-cell therapy (CAR T), a form of cancer immunotherapy.
How might the keto diet affect cancer treatment?
CAR T therapy is a personalized treatment that reprograms a patient's immune cells to attack cancer. Thousands of patients with blood cancers have benefited from this treatment, but it is not effective for everyone.
"We took an unconventional approach to improving CAR T therapy by targeting T cells through diet rather than further genetic engineering," said Shan Liu, PhD, postdoctoral fellow, and co-leader of the study.
The research team tested the effects of several diets—including the keto diet, a high-fiber diet, a high-fat diet, a high-protein diet, a high-cholesterol diet, and a control diet—on CAR T therapy's ability to fight tumors.
Using a mouse model of diffuse large B-cell lymphoma, a cancer that affects B lymphocytes, researchers discovered that mice on a ketogenic diet exhibited better tumor control and higher survival rates compared to mice on other diets.
The team found that the ketogenic diet leads to increased levels of beta-hydroxybutyrate (BHB), a molecule produced in the liver in response to ketosis, and appears to be the key factor behind the enhanced cancer-fighting power of chimeric T-cell therapy.
The ketogenic diet is a low-carbohydrate, high-fat diet designed to induce ketosis, a state in which the body uses fat as its primary energy source instead of carbohydrates. During this state, compounds known as ketones, such as beta-hydroxybutyrate (BHB), are produced, which then become the primary fuel for cells instead of glucose (sugar).
“Our theory is that chimeric T-cell therapy preferentially uses beta-hydroxybutyrate as an energy source rather than regular sugars in our bodies like glucose,” explains Puneeth Guruprasad, PhD, a medical student at the Perelman School of Medicine. “Therefore, increasing the levels of beta-hydroxybutyrate in the body gives chimeric T-cell therapy more energy to attack cancer cells.”
The team tested beta-hydroxybutyrate (BHB) supplementation in conjunction with chimeric T-cell therapy in laboratory models of human cancer, using a normal diet. The results showed complete eradication of cancer in the vast majority of mice, along with an increase in the number and activation of modified T cells.
To see if levels of beta-hydroxybutyrate in the body could have a similar effect in humans, the team analyzed blood samples from patients who had recently received chimeric T-cell therapy. They found that higher levels of beta-hydroxybutyrate were associated with an increase in the number of modified cells in these patients. They also examined T cells from healthy volunteers who took a beta-hydroxybutyrate supplement and found similar changes in how normal cells generate energy after exposure to beta-hydroxybutyrate.
The theory that beta-hydroxybutyrate supplementation may improve the response to chimeric receptor T-cell (CAR) therapy is now being tested in a phase 1 clinical trial at the Abra Mason Cancer Center at the University of Pennsylvania.
While the research is still in its early stages, the team confirmed that the results are promising. If the clinical trial proves successful, this approach could provide a low-cost and accessible option to improve the effectiveness of CAR T-cell therapy in cancer patients.