Adolescent With Metastatic Wilms Tumor Has No Detectable Active Cancer; PRAME-Targeted T-Cell Therapy to Enter Early-Stage Trial

For metastatic pediatric solid tumors that have exhausted all treatment options, achieving simultaneous regression of lesions spread across multiple organs remains a barrier that cell therapy has yet to overcome. A team in Heidelberg, Germany, has now reported that after an adolescent with relapsed, refractory Wilms tumor received PRAME-targeted T-cell therapy, imaging, tissue analysis, and liquid biopsy no longer found detectable active cancer. However, this remains the outcome of a single patient and cannot be considered proof that the therapy is effective.

The patient had cancer for approximately 10 years and underwent surgery, chemotherapy, and multiple local treatments, but the disease continued to progress. Before treatment, he had an abdominal lesion measuring approximately 16 centimeters at its longest diameter, as well as metastases in the lungs, liver, brain, and elsewhere; the pediatric oncology center’s case record also mentioned a splenic lesion. Because no standard therapies remained and he was not eligible for clinical trials at the time, the medical team sought a final treatment opportunity under a compassionate-use framework.

Testing showed that the examined tumor cells highly expressed the cancer-testis antigen PRAME, and the patient also had the HLA-A*02:01 type. The team collected autologous T cells from the patient’s blood and engineered them with a receptor provided by Immatics and encoded by the IMA203CD8 lentiviral vector, enabling the cells to recognize a PRAME-derived peptide presented on the cell surface by HLA. This therapy uses a natural T-cell receptor to recognize fragments of intracellular proteins, a mechanism different from CAR-T therapy, which directly targets cell-surface antigens. This also means the treatment is suitable only for patients with a matching HLA type and PRAME expression.

The patient received the infusion on July 2, 2025. The engineered T cells immediately expanded rapidly in the body and triggered severe cytokine release syndrome and high fever; the team brought the symptoms under control with multiple anti-cytokine treatments and steroids, after which they resolved. Early imaging initially showed pseudoprogression of lesions throughout the body, with edema also developing around the brain lesions, highlighting the acute risks and interpretive difficulties that may accompany a strong immune response.

The efficacy assessment showed consistent signals across multiple measures: a biopsy of the abdominal tumor on day 9 after infusion showed extensive T-cell infiltration and tumor necrosis; two residual lung lesions removed around day 100 contained no viable cancer cells; PET and MRI showed marked regression of lesions at all sites; and the residual abdominal and liver lesions had no metabolic activity. Tumor-derived DNA in the blood also fell below the limit of detection, and PRAME-specific T cells remained detectable in peripheral blood through day 120. The latest report therefore describes the patient as currently having no detectable active cancer, rather than declaring him cured.

The most important significance of this case is that TCR-engineered T cells may be able to overcome multiple barriers posed by solid tumors and act simultaneously against metastases in the brain and internal organs; however, this finding may still apply only to this patient. A single case cannot estimate the response rate, risk of recurrence, or rare toxicities, nor can it rule out residual cancer cells below the limit of detection. The Heidelberg team is preparing a pediatric phase 1/2 trial expected to begin in 2027, involving approximately 15 to 18 patients with relapsed or refractory solid tumors that are PRAME-positive and HLA-A*02:01-matched. Whether this deep remission can be reproduced will be the true test of whether the therapy can move beyond an individual compassionate-use case.