即时制备的PRAME特异性TCR-T细胞疗法在一例接受过多线重度预处理、患有广泛多灶性肾母细胞瘤的儿科患者中诱导深度缓解

Background: T cell receptor (TCR)-engineered T cell therapies targeting tumor-associated antigens such as PRAME have shown promising clinical activity in melanoma (Wermke, Nature Medicine, 2025). We identified high PRAME expression in multiple relapsed, refractory pediatric tumors in our pediatric precision oncology program INFORM. Here we report on a named-patient-use of transgenic PRAME-specific TCR T cells in a pediatric patient with exceeded curative treatment option, not eligible for any ongoing clinical trial. Case Description: A 17-year-old male with rapidly progressive, relapsed nephroblastoma after 2 prior systemic and multiple local lines of therapy presented in good general condition. Baseline imaging revealed a 16 cm (longest diameter) abdominal target lesion, multiple hepatic metastases (≤6 cm), bilateral pulmonary metastases and a solitary intracranial metastasis. Methods: High PRAME expression and HLA-A*02:01 status were assessed by bulk RNA sequencing and confirmed by immunohistochemistry. After written informed consent, the patient was treated under named-patient use. Autologous CD4⁺ and CD8⁺ T cells were enriched from leukapheresis, activated, and transduced with an investigational clinical-grade lentiviral vector using the CliniMACS Prodigy platform. The vector encoding a PRAME-specific TCR and a CD8alphabeta co-receptor was supplied by Immatics. After lymphodepletion with fludarabine and cyclophosphamide, freshly harvested T cells were infused at 1 × 10⁹ transduced cells/m². Results: T cell infusion led to rapid in vivo expansion, accompanied by severe cytokine release syndrome that resolved promptly with multimodal anti-cytokine therapy and corticosteroids. Early imaging demonstrated global pseudo-progression and perifocal edema of the brain lesion. An abdominal tumor biopsy on day +9 after infusion showed extensive T cell infiltration and tumor necrosis. Subsequent imaging revealed marked regression across all disease sites. Two residual pulmonary lesions resected on day +100 showed no viable tumor cells. FDG-PET demonstrated no metabolic activity in residual abdominal or hepatic lesions. Furthermore, circulating tumor-specific cell-free DNA in serum fell below the detection limit. The patient is in excellent physical condition. On day +120 PRAME-specific T cells comprised 14% of viable T cells in peripheral blood. Conclusions: Fresh point-of-care-manufactured PRAME-specific TCR T cells induced a deep antitumor response with histological, metabolic, and molecular remission evident 3 months post infusion and ongoing at 6 months follow up in a heavily pretreated pediatric patient with extensive multifocal nephroblastoma. These findings support further evaluation of PRAME-specific TCR T cell therapy in PRAME-positive pediatric cancers in a phase I/II clinical trial.