GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320375/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320375GEOGSEfalseOn-demand GLUT3 expression augments CAR-T cell metabolic fitness and antitumor efficacy whereas preventing toxicity in glioblastomaWe show that the dysfunction of CAR-T cells in GBM is attributed to glucose deficiency in the tumor microenvironment (TME) and that on-demand, but not continuous, metabolic replenishment significantly improves the antitumor efficacy of CAR-T cells. The massive consumption of glucose by cancer cells reduces the glucose level in the TME of GBM, consequently impairing CAR-T cells. Adding stable expression of glucose transporter 3 (GLUT3), a high-affinity glucose transporter, to CAR-T cells restored their cytokine production and killing activity. However, whereas CAR-T cells with stable GLUT3 expression induced tumor reduction in a GBM model, their overactivation led to adverse events and mouse death. On-demand GLUT3-expressing CAR-T cells, in which GLUT3 transcription is driven by the nuclear translocation of nuclear factor of activated T cells (NFAT) by target antigen stimulation, exhibited enhanced metabolic fitness and increased antitumor efficacy, leading to long-lasting tumor control in intracranial human GBM cell xenograft models whereas it prevented adverse events.2026/04/16GSE320375GSM9541970GSM9541971GSM9541972GSM9541973GSM9541974GSM9541963GSM9541975GSM9541964GSM9541965GSM9541976GSM9541966GSM9541977GSM9541978GSM9541967GSM9541968GSM95419692467634284320375Homo sapiens