A study published in the journal Cell on March 6, 2026, has found that β-hydroxybutyrate (BHB), a ketone body produced by the liver, can improve the effectiveness and durability of CAR T cell therapy in cancer treatment. The research was conducted by scientists from Arc Institute and Stanford University, with collaboration from the University of Pennsylvania.
Maayan Levy, Assistant Professor of Pathology at Stanford and an Arc Innovation Investigator in Residence, led the research team. According to Levy, "CAR T cell therapy has revolutionized treatment for certain blood cancers, yet many patients still fail to respond or eventually relapse. This challenge has led scientists to search for new, practical ways to strengthen T cell metabolism, without presenting additional burdens on patients."
The researchers initially tested six different diets in mice—including high-fiber, high-protein, Western, and ketogenic diets—to determine if dietary factors could influence CAR T cell efficacy. Only mice on a ketogenic diet showed consistent improvement in tumor control following CAR T therapy. Further analysis revealed that these mice had higher levels of BHB compared to other groups.
Recognizing that strict ketogenic diets are often difficult for cancer patients due to nutritional requirements and appetite loss, the team investigated whether supplementing with BHB alone would yield similar benefits. In several cancer models such as lymphoma, leukemia, and pancreatic cancer—which is typically resistant to therapy—BHB supplementation improved CAR T cell expansion and tumor killing abilities comparable to those observed with a full ketogenic diet.
Further investigation into cellular mechanisms showed that CAR T cells used BHB as an energy source by incorporating it into the mitochondrial TCA cycle. This process increased their energy production and resilience under stress. The researchers also found that BHB-treated CAR T cells consumed more oxygen and generated more ATP than standard CAR T cells.
Single-cell RNA sequencing revealed that exposure to BHB increased expression of genes linked with immune activation and tumor destruction while reducing markers associated with cellular exhaustion. Additional genomic tests indicated that BHB allowed easier access to DNA regions responsible for energy generation and immune function.
To confirm whether metabolizing BHB was necessary for its effects, the team used CRISPR gene editing to disable BDH1—the enzyme required for converting BHB into usable energy—in CAR T cells. Without this enzyme, the therapeutic improvements from BHB disappeared.
Levy stated: "The findings from this work highlight the potential of simple metabolic intervention for cancer treatment––providing CAR T cells with an efficient, naturally occurring fuel source that can meaningfully enhance their performance, even in cancers where current therapies have struggled."
While genetic engineering continues to be significant in advancing cancer treatments, this study suggests that metabolic strategies like BHB supplementation may offer scalable and cost-effective ways to support immunotherapy outcomes. A clinical trial evaluating BHB supplementation in Large B-cell Lymphoma is currently underway.
