UCLA Researchers Supercharge Immune Cells to Fight Solid Tumors

New method enables T cells to bypass glucose depletion by cancer cells, improving immunotherapy effectiveness.

Feb. 25, 2026 at 4:46am

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Researchers at UCLA have developed a way to supercharge immune cells with a fuel source that tumors can't steal, dramatically improving their ability to survive and attack solid tumors in preclinical studies. The approach involves equipping T cells with two proteins derived from fungi that allow them to import and convert cellobiose, a plant-based sugar, into usable glucose. This enables the immune cells to thrive even in the nutrient-poor tumor environment where cancer cells deplete glucose, a key limitation of current immunotherapies.

Why it matters

Solid tumors like lung, breast and colorectal cancer have proven difficult for immunotherapies to treat effectively, as the aggressive cancer cells often deplete the glucose that T cells need to function. This new approach could help overcome this metabolic roadblock, potentially benefiting the many ongoing clinical trials testing CAR-T and other T cell-based therapies for solid tumors.

The details

The researchers developed a method to feed T cells glucose without offering it to the tumor. They turned to cellobiose, a naturally occurring sugar found in plant fiber that human cells and tumors cannot break down, but some microbes and fungi can. By equipping T cells with two proteins derived from fungi, the researchers enabled the immune cells to import cellobiose and convert it into usable glucose inside the cell. In lab experiments and mouse models, these engineered T cells stayed alive, continued dividing, produced cancer-fighting cytokines, and effectively killed tumor cells, while unmodified T cells rapidly lost function.

  • The study was published in the journal Cell on February 25, 2026.

The players

Dr. Manish Butte

UCLA's E. Richard Stiehm Professor of Pediatric Allergy, Immunology and Rheumatology and a member of the UCLA Health Jonsson Comprehensive Cancer Center.

Dr. Matthew Miller

A former doctoral student in Dr. Butte's lab and now a postdoctoral fellow at the Salk Institute.

UCLA

The university where the research was conducted.

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What they’re saying

“We demonstrate not only that glucose can be a limiting component of an effective anti-tumor response, but that we can design strategies to bypass the metabolic tug-of-war and deliver a high-value nutrient to T cells engineered with the proprietary metabolic processing system.”

— Dr. Matthew Miller, Former doctoral student in Dr. Butte's lab, now postdoctoral fellow at the Salk Institute (Cell)

“The survival of T cells in minimal levels of glucose was a huge hint that this was going to work. We saw that when glucose was scarce, the modified T cells used cellobiose to power all the same core energy pathways they normally use glucose for. Their metabolism looked healthy and normal, not starved.”

— Dr. Manish Butte, UCLA's E. Richard Stiehm Professor of Pediatric Allergy, Immunology and Rheumatology (Cell)

What’s next

The researchers believe adding the two genes that enable T cells to metabolize cellobiose, along with controlled delivery of cellobiose, could help many of the over 500 ongoing clinical trials testing CAR-T and other T cell-based therapies for solid tumors.

The takeaway

This new approach to supercharge immune cells with a tumor-resistant fuel source has the potential to significantly improve the effectiveness of T cell-based immunotherapies for solid tumors, which have proven difficult to treat effectively due to the metabolic competition between cancer cells and immune cells.