Sodium-Glucose Cotransporter SGLT2 Supports Metabolic Fitness and Ferroptosis Resistance in CAR-T Cells to Enhance Activity Against Solid Tumors.

Overexpression of SGLT2 in CAR-T cells enhances glycolysis, mitochondrial fitness, and antitumor activity against solid tumors by increasing glucose and NaCl uptake.

• Why it matters: Solid tumor microenvironments impair CAR-T cell function through glucose deprivation and high NaCl, limiting their effectiveness. Improving CAR-T cell metabolism could overcome these barriers and improve therapy outcomes.
• What they did: Researchers engineered CAR-T cells to overexpress SGLT2, a sodium-glucose cotransporter, and tested their activity in multiple solid tumor xenograft models, focusing on metabolic and functional improvements.
• The result: SGLT2 overexpression boosted glycolysis, mitochondrial health, and activated the AKT-mTOR pathway, leading to stronger antitumor responses and ferroptosis resistance, suggesting a promising metabolic engineering approach.