GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324103/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324103GEOGSEfalseViscoelasticity reprograms T cell metabolism for TCR-T cell manufacturing and therapyAdoptive 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.2026/09/03GSE324103GSM9568285GSM9568286GSM9568287GSM9568288GSM9568289GSM9568300GSM9568280GSM9568281GSM9568282GSM9568283GSM9568284GSM9568296GSM9568274GSM9568275GSM9568297GSM9568298GSM9568276GSM9568299GSM9568277GSM9568278GSM9568279GSM9568290GSM9568291GSM9568292GSM9568293GSM9568294GSM95682952467634284324103Homo sapiens