Background: Cancer immunotherapy with engineered T cells has become a standard treatment for certain haematological cancers. However, clinical trial outcomes for solid tumours are significantly lagging. A primary challenge in solid tumours is the lack of essential metabolites in the tumour microenvironment, such as glucose, due to poor vascularization and competition with tumour cells.
Methods: To address this, we modified T cells to use fructose as an alternative energy source by introducing ectopic GLUT5 expression.
Results: We show that "GLUT5-armored" T cells, engineered with either chimeric antigen receptors (CARs) or an ectopic T-cell receptor (TCR), achieve enhanced anti-tumour activity in low-glucose environments in both in vitro and in vivo models.
Conclusion: This straightforward modification is compatible with current clinical approaches and may improve the efficacy of T-cell therapies for solid tumours.
Keywords: CAR T cells; immunometabolism; immunotherapy.
© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Immunology.