GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325706/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325706GEOGSEfalseGPNMB as a viable CAR Target for MITF pathognomonic fusion-driven cancers: A first-in-person GCAR1 Trial [ASPS-02_VisiumHD]CAR T therapy for solid tumours is limited by a lack of safe and uniformly expressed cell-surface targets. We identify the MITF-driven gene GPNMB as being highly, homogeneously and stably expressed from primary and relapsed translocation-positive alveolar soft part sarcoma (ASPS) and renal cell carcinoma (tRCC). We developed a 2nd generation GPNMB-targeting CAR T therapy (GCAR1) that shows activity against cells, organoids and PDX models. First-in-person GCAR1 treatment of a patient with metastatic ASPS was well tolerated and generated stable disease for 6 months, with the majority of non-target lung lesions resolving post-treatment. A diverse population of GCAR1 cells expanded in blood, peaking at 14 days post-treatment. Spatial transcriptomics revealed immunosuppression, including PDL1 expression, in close proximity to T cells infiltrating a treatment-resistant lung lesion, and PDL1 blockade showed synergy with GCAR1 in a PDX model. Our data provide a proof-of-concept for targeting oncogenic translocation-driven genes with CAR T therapy.2026/04/02GSE325706GSM9610990GSM961099130173325706Homo sapiens