{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320375/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320375"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"On-demand GLUT3 expression augments CAR-T cell metabolic fitness and antitumor efficacy whereas preventing toxicity in glioblastoma","description":"We 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.","dates":{"publication":"2026/04/16"},"accession":"GSE320375","cross_references":{"GSM":["GSM9541970","GSM9541971","GSM9541972","GSM9541973","GSM9541974","GSM9541963","GSM9541975","GSM9541964","GSM9541965","GSM9541976","GSM9541966","GSM9541977","GSM9541978","GSM9541967","GSM9541968","GSM9541969"],"GPL":["24676","34284"],"GSE":["320375"],"taxon":["Homo sapiens"]}}