GLUT5 armouring enhances adoptive T-cell therapy anti-tumour activity under glucose-limiting conditions.

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.