{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324103/"]},"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=GSE324103"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Viscoelasticity reprograms T cell metabolism for TCR-T cell manufacturing and therapy","description":"Adoptive T cell receptor (TCR)–based immunotherapy offers a powerful strategy to target solid tumors through recognition of either cell surface antigens or intracellular tumor antigens. However, the ex vivo generation of metabolically fit, durable T cells capable of sustained function in the immunosuppressive solid tumor microenvironment remains a major bottleneck. While dendritic cell–based antigen presentation can provide physiological activation signals, its clinical translation is limited by donor variability, poor scalability, uncontrolled paracrine signaling, and the risk of T cell exhaustion. Here we develop synthetic viscoelastic activating cells (SynVAC)—a class of artificial antigen-presenting cells (aAPCs) whose stress-relaxation kinetics are independently and precisely tuned while maintaining constant stiffness and defined densities of peptide–major histocompatibility complex (pMHC) and co-stimulatory ligands. SynVAC-pMHC offers a well-defined and scalable platform that outperforms monocyte-derived dendritic cells (moDCs) to enrich antigen-specific CD8+ T cells. Particularly, fast-relaxing SynVAC-pMHC amplifies TCR signaling and mTOR activity, drives mitochondrial remodeling, and programs antigen-specific T cells toward an energetically favorable metabolic state with enhanced stem-like properties. Furthermore, TCR-T cells expanded using fast-relaxing SynVAC-pMHC exhibit superior persistence and durable antitumor activity in melanoma and ovarian cancer models. Together, these results establish cell-mimetic viscoelasticity as a key biophysical cue governing T cell metabolism and differentiation, and provide a scalable, fully synthetic strategy to manufacture potent TCR-T cells for solid tumor therapy.","dates":{"publication":"2026/09/03"},"accession":"GSE324103","cross_references":{"GSM":["GSM9568285","GSM9568286","GSM9568287","GSM9568288","GSM9568289","GSM9568300","GSM9568280","GSM9568281","GSM9568282","GSM9568283","GSM9568284","GSM9568296","GSM9568274","GSM9568275","GSM9568297","GSM9568298","GSM9568276","GSM9568299","GSM9568277","GSM9568278","GSM9568279","GSM9568290","GSM9568291","GSM9568292","GSM9568293","GSM9568294","GSM9568295"],"GPL":["24676","34284"],"GSE":["324103"],"taxon":["Homo sapiens"]}}