GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325772/primaryOK200TranscriptomicsHomo sapiens OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325772GEOGSEfalseCAR T therapy against the MiTF-driven protein GPNMB [Multiome-Seq]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.2026/04/02GSE325772GSM9613158GSM9613159GSM9613154GSM9613165GSM9613155GSM9613156GSM9613157GSM9613161GSM9613150GSM9613162GSM9613151GSM9613163GSM9613152GSM9613164GSM9613153GSM961316024676325772Homo sapiens