{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330395/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Methylation profiling"],"species":["Homo sapiens"],"gds_type":["Methylation profiling by genome tiling array"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330395"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Clinical development of tacrolimus-resistant regulatory T cells to enable simultaneous immunosuppression and support of immune regulation","description":"Unwanted alloimmune responses are a central driver of solid organ transplant rejection and currently managed with life-long immunosuppression, which imposes substantial risks and burdens on patients. Adoptive transfer of regulatory T cells (Tregs) offers a strategy to restore immunological balance and reduce long-term adverse effects of generalized immunosuppression. However, while Tregs can potently inhibit incipient immune activation, they struggle to suppress established memory effector T cells, necessitating the continued use of immunosuppression. Calcineurin inhibitors such as Tacrolimus effectively control both, newly activated and pre-existing effector-T-cells, but unfortunately, they also impair Treg function. Therefore, we hypothesized that gene-editing of Tregs inducing Tacrolimus resistance (FKBP12KO) would enable combined therapy that curbs effector T-cell responses without compromising Treg efficacy. Here, we developed FKBP12KO-Tregs using a ribonucleoprotein-based CRISPR/Cas9 approach and characterized them extensively in-vitro. FKBP12KO-Tregs retained phenotype, high viability, and suppressive function comparable to unedited TregWT and they remained functionally impervious to Tacrolimus, while preserving sensitivity to alternative CNIs. We additionally established a Good-Manufacturing-Practice process for FKBP12KO-Tregs. Comprehensive in vitro phenotypic, functional, and molecular characterization, together with the established manufacturing, provide the rationale for a proof-of- concept clinical trial assessing the feasibility and safety of co-administration of FKBP12KO-Tregs with Tacrolimus in living-donor kidney transplant recipients.","dates":{"publication":"2026/06/11"},"accession":"GSE330395","cross_references":{"GSM":["GSM9725320","GSM9725321","GSM9725310","GSM9725311","GSM9725322","GSM9725312","GSM9725313","GSM9725314","GSM9725315","GSM9725316","GSM9725317","GSM9725318","GSM9725307","GSM9725319","GSM9725308","GSM9725309"],"GPL":["21145"],"GSE":["330395"],"taxon":["Homo sapiens"]}}