Scientists report a remarkable response to a personalized T-cell therapy in a teenager with a metastatic, treatment-resistant kidney tumor. Results published today in the New England Journal of Medicine show no evidence of active disease one year after treatment, highlighting the therapy’s potential ahead of an upcoming clinical trial.
The patient was first 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 received the personalized T-cell therapy, the cancer had spread extensively across the abdominal cavity, lung, liver, pelvis, and brain. With no curative treatment options or suitable clinical trials available at the time, he received the therapy on a compassionate-use basis.
Through the INFORM tumor sequencing program, the researchers identified the expression of the PRAME antigen in the patient’s tumor. Although this antigen is linked to high tumor proliferation and poorer prognosis across multiple cancer types, it also offered a potential target for personalized treatment.
“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 the Hopp Children’s Cancer Center Heidelberg (KiTZ) and Heidelberg University Hospital (UKHD). “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. In clinical trials in adults, impressive treatment successes have already been achieved with PRAME-specific T cells.”
Scientists at the National Center for Tumor Diseases (NCT) in Heidelberg genetically modified the patient’s own T cells to recognize PRAME, using a vector provided by Immatics. Nine days after treatment, a tumor biopsy revealed a dramatic increase in T-cell infiltration within the tumor and signs of cancer cell death. The cancer continued to regress across all organs until, three months later, biopsies, imaging and blood tests showed complete tumor regression.
“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,” said Seitz. “The case demonstrates the potential that innovative immunotherapies can unfold for children and adolescents with previously incurable tumor diseases.”
This remarkable response comes as preparations advance for a Phase I/II clinical trial that will recruit up to 18 children and adolescents with PRAME-positive solid tumors. Planned to begin in 2027, the study will provide an opportunity to assess whether the results seen in this one patient can be replicated in other young people with cancer.
“Tumor data from more than 2,500 patients from our INFORM study show that this protein occurs in many high-risk tumors in children and adolescents and therefore represents a promising target for new therapies,” said Olaf Witt, MD, co-lead of the upcoming clinical trial and director of KiTZ.
