{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE282nnn/GSE282057/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":[" Mus musculus","Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282057"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"GPNMB as a viable CAR Target for MITF pathognomonic fusion-driven cancers: A first-in-person GCAR1 Trial","description":"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.","dates":{"publication":"2026/04/02"},"accession":"GSE282057","cross_references":{"GSM":["GSM8634986","GSM8634989","GSM8634987","GSM8634988"],"GPL":["30173","30172"],"GSE":["282057"],"taxon":[" Mus musculus","Homo sapiens"]}}