Researchers report encouraging early results from a first-in-human clinical trial led by Children's National using a new T-cell immunotherapy for children and young adults with some of the deadliest brain tumors, including diffuse intrinsic pontine glioma (DIPG) and relapsed central nervous system (CNS) tumors. These findings, published in Nature Medicine , are particularly significant given the challenges faced in treating pediatric brain tumors, which remain the leading cause of cancer-related deaths in children. Immunotherapies have been shown to work in blood cancers but rarely succeed in solid tumors, especially brain tumors.
"This study represents an important step toward developing safer and more effective T-cell therapies for children with devastating brain cancers," said Catherine Bollard, MBChB, MD , senior vice president and chief research officer at Children's National, and co-senior author of the study. "Even in this early-stage trial focused on safety, we were encouraged to see lasting clinical benefit in several patients who otherwise had very few options."
The Phase 1 study evaluated a novel multi-targeted T-cell therapy designed to strike three proteins commonly found in pediatric brain tumors – WT1, PRAME and Survivin. Investigators say the results provide early evidence that the patient's own immune cells delivered through the bloodstream can reach and fight tumors in the brain while producing fewer severe side effects than some existing engineered immune therapies. Many other brain tumor immunotherapies require direct injection into the brain or cerebrospinal fluid.
"We were excited to see that we could preserve safety and quality of life while generating anti-tumor responses by attacking three targets at once," said Eugene Hwang, MD , chief of Oncology at Children's National and co-senior author of the study.
Key takeaways:
- The multi-target design may help address tumor heterogeneity, one of the major barriers to successful treatment of aggressive childhood cancers.
- The trial successfully established a feasible manufacturing process, identified a maximum tolerated dose and defined an early safety profile – key milestones needed to advance the therapy into future Phase 2 studies.
- Researchers analyzed patients with DIPG or relapsed brain cancers, showing both responses and prolonged disease control, with some patients remaining disease-free years after treatment.
"We are so proud of the team at Children's National and inspired by what this breakthrough means for children with brain cancer," said Callie and Brad Nierenberg, founders of Chance for Life, which helped to fund the study. "Supporting this trial has been one of the most meaningful investments Chance for Life has made."
"Pediatric tumors are one of the greatest challenges in cancer research, with children still facing extremely limited treatment options, and existing treatments often causing severe side effects," said David Scott, director of Cancer Grand Challenges, which supports the NexTGen team, a group of international collaborators co-led by Dr. Bollard that is taking on the 'solid tumors in children' Cancer Grand Challenge.
This research was also supported by generous funders reflecting the strength of the community in fighting these deadly cancers, including: the Chance for Life Foundation; anonymous private investors supporting the Children's National Hospital Brain Tumor Institute; Cancer Research UK, the National Cancer Institute and The Mark Foundation for Cancer Research, through the Cancer Grand Challenges award (NCI/CRUK OT2CA278700); the GW T32 Cancer Biology Program (NIH/NCI T32 CA247756); the Rally Foundation; the Willie Strong Foundation; and the Warrior Jace Foundation.
