{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325772/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":[" Other","Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325772"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CAR T therapy against the MiTF-driven protein GPNMB [Multiome-Seq]","description":"CAR T therapy for solid tumors is constrained by the scarcity of safe, uniformly expressed cell-surface targets. Here we identify GPNMB, a MiT fusion-driven protein, as highly, homogeneously, and stably expressed in primary and relapsed translocation-positive alveolar soft part sarcoma (ASPS) and renal cell carcinoma (tRCC). We develop a GPNMB-directed CAR T cell product, GCAR1, which demonstrates potent activity against patient-matched cells, organoids and xenograft models. In a first-in-human treatment of two patients with relapsed/refractory, metastatic ASPS, GCAR1 is well tolerated and induces stable disease for up to 6 months, accompanied by resolution of many non-target lesions. GCAR1 T cells expand in peripheral blood as a polyclonal population and remain detectable for up to 6 months. Spatial transcriptomics identify multiple immunosuppressive niches adjacent to T cells infiltrating treatment-resistant lesions; biological PDL1 blockade or PD1 and TIGIT double knockout overcomes this resistance and shows synergistic activity with GCAR1 in xenograft models. Taken together, these data provide clinical proof-of-concept for treating solid tumors with CAR T cells targeting a surface antigen driven by an oncogenic gene fusion.","dates":{"publication":"2026/04/02"},"accession":"GSE325772","cross_references":{"GSM":["GSM9613158","GSM9613159","GSM9613165","GSM9613154","GSM9613155","GSM9613156","GSM9613157","GSM9613161","GSM9613150","GSM9613162","GSM9613151","GSM9613163","GSM9613152","GSM9613164","GSM9613153","GSM9613160"],"GPL":["24676"],"GSE":["325772"],"taxon":["Homo sapiens"]}}