{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293800/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293800"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Cancer agnostic potential of CAR T cells targeting the urokinase plasminogen activator receptor","description":"Chimeric Antigen Receptor (CAR) T cells have demonstrated transformative efficacy in hematologic malignancies and have shown promise in non-cancer contexts such as autoimmune diseases. We previously identified the urokinase plasminogen activator receptor (uPAR) as a cell-surface protein expressed on subsets of myeloid cells and broadly upregulated in senescent states. Murine uPAR-targeting CAR T cells can ameliorate fibrosis and prophylactically prevent metabolic syndrome in aged mice, paving the way for their use in senescence-driven pathologies. uPAR can also be expressed at high levels in cancer and, by performing a pan-cancer analysis, we now show that subsets of most tumor types display strong uPAR expression, which correlates with an epithelial-mesenchymal transition (EMT)-like state, increased fibrosis, metastasis, and poor patient outcomes. Single-cell and spatial analyses revealed that tumors with high uPAR expression in tumor cells often harbor senescent-like, uPAR-positive stromal cells, typically subsets of fibroblasts and macrophages. In mouse models, CAR T cells with uPAR-targeting single-chain variable fragments (scFvs) showed potent and persistent efficacy against multiple tumor types. In the context of high-grade serous ovarian cancer, adjuvant CAR T cell treatment following primary tumor debulking surgery cured mice by eliminating distal organ metastases. uPAR CAR T cells were well-tolerated, demonstrating efficacy in syngeneic and humanized immune system models without significant disruption of the myeloid compartment. Beyond direct tumor targeting, uPAR facilitated non-invasive cancer monitoring via soluble uPAR and PET imaging. Senescence-inducing therapies further enhanced uPAR expression and showed combinatorial activity with uPAR CAR T cells. These findings establish uPAR CAR T cells as a cancer-agnostic therapeutic strategy with a favorable safety profile and clear clinical potential in oncology, including solid tumors harboring a fibrotic tumor microenvironment linked to accumulation of senescent stromal cells.","dates":{"publication":"2026/03/31"},"accession":"GSE293800","cross_references":{"GSM":["GSM8890214"],"GPL":["33762"],"GSE":["293800"],"taxon":["Homo sapiens"]}}