Researchers at the Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital, the German Cancer Research Center (DKFZ), and collaborating institutions have reported an extraordinary response to personalized T-cell therapy in an adolescent with advanced, treatment-resistant nephroblastoma, also known as Wilms tumor. After ten years of repeated relapses and the spread of cancer to several organs, the patient received genetically modified versions of his own immune cells in an individual compassionate-use treatment. Within months, physicians could no longer detect living tumor cells in biopsy samples, while imaging and blood tests showed no evidence of active disease. The case, published in the New England Journal of Medicine, offers a striking example of how cellular immunotherapy might be adapted for children with solid tumors that have exhausted conventional treatment options.
The patient was diagnosed with a kidney tumor at the age of seven. Over the following decade, the disease returned repeatedly and developed widespread metastases. By the time he was considered for the experimental treatment, large tumor masses had formed in the abdominal cavity, while additional lesions were present in the lungs, liver, pelvis, and brain. Standard therapies had failed to produce a durable cure, and no suitable clinical trial or established treatment option remained. Molecular profiling performed through the INFORM pediatric tumor-sequencing program identified a potentially exploitable feature of the cancer: the tumor cells produced PRAME, short for Preferentially Expressed Antigen in Melanoma, a protein that is normally absent or present only at very low levels in most healthy tissues but is frequently activated in cancer.
PRAME has attracted considerable interest as an immunotherapy target because its restricted distribution in normal tissues may create a therapeutic window. The protein is found in a range of adult malignancies, including melanoma, sarcomas, and several other aggressive cancers. It has also been detected in high-risk pediatric tumors. In the INFORM database, which includes molecular data from more than 2,500 children and adolescents with cancer, PRAME appears in many tumors for which treatment options are limited. The protein is produced inside cancer cells and can be processed into short fragments that are displayed on the cell surface by human leukocyte antigen molecules. T cells equipped with a suitable antigen-recognition system can potentially identify these fragments and destroy the cells presenting them.
The Heidelberg team used the patient’s own T cells as the starting material for the treatment. In the laboratory, the cells were genetically modified so that they could recognize PRAME on tumor cells and mount a targeted immune response. The genetic instructions were delivered using a vector supplied by Immatics, a biotechnology company based in Tübingen that has developed PRAME-directed T-cell platforms and has tested related approaches in adults. The modified cells were manufactured locally at the National Center for Tumor Diseases in Heidelberg in a seven-day process. After preparatory treatment to create space for the infused cells within the immune system, the patient received the personalized cellular product in July 2025.
The biological response was visible almost immediately. Nine days after infusion, a biopsy of a tumor lesion revealed extensive infiltration by the engineered T cells. The sample also showed widespread death of malignant cells, suggesting that the modified immune cells had reached the tumor and were actively exerting their intended effect. During the weeks and months that followed, tumor deposits regressed across all affected organs. A second biopsy, obtained three months after treatment, contained no detectable living tumor cells. Serial imaging studies and blood analyses have since found no evidence of active cancer, according to the treating physicians. The report does not establish that the patient is permanently cured, but the depth and breadth of the response are highly unusual in a disease that had continued to progress despite multiple lines of therapy.
Almost a year after the infusion, the patient, identified in accompanying materials as Mailo, was reported to be in excellent physical condition. He has resumed regular mountain-bike training and participated in cycling competitions, completed his vocational training, and is preparing to pursue his Abitur, the German university-entrance qualification. Such recovery is especially notable given the extent of his disease before treatment. At the same time, the investigators emphasize that this is a single compassionate-use case rather than evidence that PRAME-specific T-cell therapy is effective for all pediatric cancers. Responses can depend on the amount of target antigen expressed by a tumor, the patient’s HLA type, the ability of engineered cells to enter solid tumor tissue, and the capacity of cancer cells to evade immune recognition.
The treatment also illustrates the technical challenges of bringing cell therapy to children with solid tumors. Unlike many blood cancers, solid tumors are embedded in complex tissue environments that can restrict immune-cell entry and suppress T-cell activity. Tumor cells may lose or reduce the target antigen, alter antigen presentation, or create an immunosuppressive environment that limits cellular persistence. The Heidelberg biopsy results are therefore important because they provided direct evidence that the engineered cells penetrated the tumor and were associated with malignant-cell destruction. Further studies will need to determine how long the modified T cells remain in the body, whether they establish immune memory, and how frequently resistance or relapse occurs after an initial response.
Building on the case, KiTZ is preparing a first Phase I/II clinical trial called PRAMEtime for children and adolescents with PRAME-positive solid tumors. The study is planned to enroll up to 18 patients between eight and 17 years of age, with a projected start in 2027. Participants will receive their own genetically modified immune cells, produced through the collaboration with Immatics. In future projects, manufacturing is expected to be supported by the Center for Innovative Therapies in Heidelberg, established by Heidelberg University Hospital and the DKFZ in June 2026, while Immatics will continue to provide the vector used to reprogram T cells for PRAME-positive tumors. The early-phase trial will primarily assess safety, feasibility, dosing, cellular persistence, and preliminary signs of antitumor activity.
The PRAMEtime program is being supported by approximately 1.8 million euros from the Dietmar Hopp Foundation over four years at the Heidelberg Medical Faculty of Heidelberg University. Academic funding is particularly important in pediatric oncology, where individual tumor types are rare and patient populations are too small to attract extensive commercial investment. The project also demonstrates the increasingly interdependent relationship between biotechnology companies and academic hospitals: industry partners can supply sophisticated molecular tools and vectors, while specialist cancer centers identify suitable patients, manufacture cellular products, perform intensive monitoring, and investigate the biological reasons for response or treatment failure. If the planned trial confirms that PRAME-directed cells can be administered safely and repeatedly benefit children with otherwise incurable solid tumors, the approach could become a foundation for broader pediatric cellular-immunotherapy studies. For now, the adolescent’s recovery remains an exceptional result—but one that has transformed a promising laboratory target into a clinically testable strategy for a group of patients with few remaining options.
Subject of Research: Personalized PRAME-specific genetically modified T-cell therapy for advanced, treatment-resistant pediatric nephroblastoma and other PRAME-positive solid tumors.
Article Title: PRAME-Specific T-Cell Therapy in Advanced Pediatric Nephroblastoma
News Publication Date: 13 August 2026
Web References: https://doi.org/10.1056/NEJMc2605154
References: K. Mair et al., “PRAME-Specific T-Cell Therapy in Advanced Pediatric Nephroblastoma,” New England Journal of Medicine, online publication 13 August 2026. DOI: 10.1056/NEJMc2605154
Image Credits: Image 1: private. Image 2: @mailo.grh.
Keywords: pediatric cancer, nephroblastoma, Wilms tumor, PRAME, T-cell therapy, cellular immunotherapy, gene-modified T cells, solid tumors, personalized medicine, immuno-oncology, KiTZ Heidelberg, DKFZ, Immatics, compassionate use, PRAMEtime
