UCLA researchers give T cells a fuel tumors can't steal

UCLA researchers engineered T cells to import and process cellobiose, a sugar tumors cannot use; in lab and mouse studies the modified cells remained active, produced cytokines and improved tumor control.

UCLA researchers report a method to feed engineered T cells a sugar that tumors cannot use. They equipped T cells with two fungal-derived proteins that let the immune cells import cellobiose and convert it into usable glucose inside the cell. In laboratory and mouse studies, these modified T cells survived, proliferated, produced cytokines such as IFN-γ and TNF, and showed improved tumor control compared with unmodified cells. The work was published in Cell and received support from NIH and several foundations. Key findings: - Engineered T cells carried two fungal-derived proteins that enabled import and intracellular processing of cellobiose into glucose. - Human cells and tumor cells cannot break down cellobiose; the sugar is commonly used in foods and is described as generally regarded as safe by the U.S. Food and Drug Administration. - In low-glucose laboratory conditions that mimic solid-tumor environments, modified T cells remained viable, proliferated, produced IFN-γ and TNF, and effectively killed tumor cells while unmodified T cells lost function. - In mouse models, animals given tumor-targeted T cells able to metabolize cellobiose showed slower tumor growth, longer survival, and some complete tumor regressions. - Human CAR-T cells tested in low-glucose lab conditions regained survival, cytokine production and tumor-killing activity when given access to cellobiose, and showed a trend toward improved tumor control in mice. Summary: The findings show a method to bypass tumor-driven glucose shortage and improve T cell metabolic fitness in preclinical models. The approach restored anti-tumor activity in laboratory and mouse experiments and could be applicable to multiple T cell–based therapies. Undetermined at this time.