{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE283nnn/GSE283385/"]},"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=GSE283385"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CAR T therapy against the MiTF-driven protein GPNMB","description":"CAR T therapy for solid tumors is limited by a lack of safe and uniformly expressed cell-surface targets. Here, we identify the MiTF-driven protein GPNMB as being highly, homogeneously, and stably expressed from primary and relapsed translocation-positive alveolar soft part sarcoma (ASPS) and renal cell carcinoma. We developed a GPNMB-targeting CAR T therapy called GCAR1 that shows activity against patient-matched cells, organoids and xenograft models. First-in-human treatment of a patient with metastatic ASPS was well tolerated and generated stable disease until 6 months, with many non-target lesions resolving post-treatment. A polyclonal population of GCAR1 cells expanded in blood and were detectable until 6 months. Spatial transcriptomics revealed multiple immunosuppressive niches in proximity to T cells infiltrating a treatment-resistant lesion, and PDL1 blockade showed synergy with GCAR1 in a xenograft model. Our data provide clinical evidence for treating solid tumors with CAR T cells targeting a surface protein driven by an oncogenic gene fusion.","dates":{"publication":"2026/04/02"},"accession":"GSE283385","cross_references":{"GSM":["GSM8661247","GSM8661257","GSM8661246","GSM8661245","GSM8661256","GSM8661244","GSM8661255","GSM8661249","GSM8661248","GSM8661250","GSM8661254","GSM8661253","GSM8661252","GSM8661251"],"GPL":["24676"],"GSE":["283385"],"taxon":["Homo sapiens"]}}