PRAME-Directed TCR Cell Therapy Achieves Deep Remission in Pediatric Nephroblastoma Patient
核心洞察
A 17-year-old patient with advanced metastatic nephroblastoma (搜索) achieved deep remission following treatment with Immatics' PRAME (搜索)-directed TCR T-cell therapy at KiTZ (搜索) in Heidelberg.
The patient had rapidly progressing disease with brain, liver, and lung metastases and had exhausted all available treatment options before receiving the experimental therapy.
PET scan and MRI imaging demonstrated marked tumor regression across all lesion sites, with molecular remission confirmed by liquid biopsy showing no tumor-derived DNA.
A 17-year-old patient with advanced metastatic nephroblastoma (搜索) has achieved deep and durable remission following treatment with a PRAME (搜索)-directed TCR T-cell therapy using Immatics' technology at the Hopp Children's Cancer Center Heidelberg (搜索) (KiTZ (搜索)). The case represents a significant breakthrough for pediatric cancer (搜索) treatment and will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2026.
Remarkable Response in Terminal Case
The adolescent patient presented with rapidly progressing PRAME (搜索)-positive nephroblastoma (搜索), a malignant kidney cancer (搜索) that predominantly affects children. The disease had metastasized extensively to the lung, liver, and brain, with an abdominal lesion measuring 16 cm in longest diameter. After exhausting all available treatment options and being ineligible for ongoing clinical trials, the treating physician requested Immatics' PRAME-directed TCR for an individual experimental treatment attempt.
The patient experienced a profound anti-tumor response following treatment with the TCR T-cell therapy manufactured at KiTZ (搜索) using Immatics' IMA203CD8 lentiviral vector. Remission was observed three months post-infusion and remained ongoing at six months of follow-up. PET scan and MRI imaging demonstrated marked tumor regression across all lesion sites, while liquid biopsy monitoring showed no detectable tumor-derived DNA, indicating molecular remission.
"We are very grateful to Immatics for providing the PRAME (搜索)-directed TCR that enabled us to reprogram the pediatric patient's cells," said Christian M. Seitz, M.D., treating physician and Group Leader of the Translational Immunotherapy group at KiTZ (搜索). "We hope that possible further clinical evaluation may demonstrate the potential of PRAME-targeted cellular immunotherapies in helping other children and adolescents with cancer (搜索), as seen in this patient."
Safety Profile and Clinical Management
The treatment was associated with cytokine release syndrome (搜索), which was manageable and resolved under multi-modal anti-cytokine therapy and corticosteroids. At six months of follow-up, the patient remained in excellent physical condition, demonstrating the therapy's potential for achieving durable responses with manageable toxicity.
PRAME as Pediatric Cancer Target
PRAME (搜索) is expressed on the cell surface of more than 50 cancers and represents a particularly promising target for pediatric malignancies. Based on high PRAME expression across multiple pediatric tumors and the potential for particularly strong immune responses in young patients, PRAME TCR T-cell therapies may offer a new treatment paradigm for these patients.
"Seeing such a profound response in a pediatric patient who had no treatment options left is both remarkable and deeply encouraging," said Cedrik Britten, M.D., Ph.D., Chief Medical Officer at Immatics. "It reinforces our belief in PRAME (搜索) as a powerful target and highlights the potential of cell therapy for pediatric cancers, where tumors often show high PRAME expression."
Clinical Development Plans
Immatics is planning to evaluate the potential of its PRAME (搜索) TCR T-cell therapy candidates in pediatric patients with cancer (搜索). The company is assessing multiple options for clinical development, including a potential first-in-pediatrics Phase 1/2 basket study in pediatric patients with HLA-A*02:01 (搜索)-positive, PRAME-expressing relapsed or refractory solid tumors at KiTZ (搜索) in Heidelberg.
The company's PRAME (搜索)-directed TCR T-cell therapies are engineered to recognize an intracellular PRAME-derived peptide presented by HLA-A*02:01 (搜索) on tumor cell surfaces and initiate potent, specific anti-tumor responses. Immatics currently maintains the broadest PRAME franchise, with multiple clinical-stage programs spanning cell therapies and bispecifics across adult cancer (搜索) populations.
The lead PRAME (搜索) cell therapy candidate, anzu-cel (搜索) (anzutresgene autoleucel (搜索), IMA203), is currently being evaluated in a registration-enabling Phase 3 trial "SUPRAME" in previously treated advanced cutaneous melanoma (搜索) and a Phase 2 trial in metastatic uveal melanoma (搜索). The second-generation PRAME cell therapy, IMA203CD8, is being evaluated in a Phase 1a dose escalation trial in patients with PRAME-positive solid tumors, with a focus on gynecologic cancers (搜索).