A 17-year-old patient with advanced metastatic nephroblastoma achieved complete molecular and clinical remission following an experimental T-cell receptor therapy directed against the PRAME antigen.
Medical researchers and clinicians in Germany have documented a remarkable response in a teenager suffering from a rapidly progressing, treatment-resistant kidney tumor. The case, which highlights the expanding horizon of cellular immunotherapy, utilized a personalized T-cell receptor (TCR) therapy designed to target a specific protein found across numerous high-risk solid tumors.
Advanced Disease and the Decision for Compassionate Use
The patient was initially diagnosed with a kidney tumor at age seven and went on to experience multiple relapses and metastases over the following decade. By the time he reached adolescence, the cancer had advanced to a severe stage. He presented with a bulky, rapidly progressing nephroblastoma—a malignant kidney cancer that predominantly occurs in children—featuring an abdominal lesion measuring 16 centimeters in longest diameter alongside widespread metastases to the lung, liver, and brain.
With all standard treatment options exhausted and no open clinical trials available for his specific profile, the treating physician requested an individual experimental treatment attempt, known in Germany as an Individueller Heilversuch
, on a compassionate-use basis. The intervention was coordinated at the Hopp Children’s Cancer Center Heidelberg (KiTZ) and Heidelberg University Hospital (UKHD).
Targeting PRAME via Immatics Vector Technology
To find a therapeutic vulnerability, researchers utilized the INFORM tumor sequencing program. The sequencing revealed the expression of the PRAME antigen in the patient’s tumor. Although this antigen is typically linked to high tumor proliferation and poorer prognoses in adult cancers like malignant melanoma, it provided a precise target for engineered cellular therapy.
PRAME is well described as a target structure for immunotherapies in adult cancers, for example malignant melanoma,
said Christian M. Seitz, MD, head of the stem cell transplantation, cell and gene therapy program at KiTZ and Heidelberg University Hospital. Our decision to offer the treatment despite the far advanced disease was based on highly promising clinical data from our collaboration partner Immatics, a biotechnology company based in Tübingen.
Just nine days after the infusion, a tumor biopsy revealed a dramatic increase in T-cell infiltration accompanied by clear indicators of cancer cell death.
Clinical Remission and Ongoing Recovery
The therapeutic response unfolded rapidly across all affected organ sites. Three months post-infusion, imaging via PET scans and MRIs demonstrated marked tumor regression. Furthermore, liquid biopsy monitoring showed no detectable tumor-derived DNA, signaling a complete molecular remission.
“At the present time, one year after the infusion of the T cells, our patient is in excellent condition. He trains regularly, takes part in cycling races, and was able to successfully complete his vocational training.”
Christian M. Seitz, MD, group leader of the translational immunotherapy group at KiTZ
Implications for Future Pediatric Clinical Trials
The successful outcome in this adolescent case has catalyzed broader clinical development plans. Consequently, investigators view it as a compelling target for young patients who otherwise face dismal prognoses.
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