GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE283nnn/GSE283385/primaryOK200TranscriptomicsHomo sapiens OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE283385GEOGSEfalseCAR T therapy against the MiTF-driven protein GPNMBCAR 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.2026/04/02GSE283385GSM8661247GSM8661257GSM8661246GSM8661245GSM8661256GSM8661255GSM8661244GSM8661249GSM8661248GSM8661250GSM8661254GSM8661253GSM8661252GSM866125124676283385Homo sapiens