Advances in Pediatric Cancer: CAR-T Therapy, mRNA Vaccine, Biomarker Show Promise
A first-in-human T-cell therapy showed lasting benefit in children with DIPG and relapsed CNS tumors, while a preclinical mRNA vaccine reduced neuroblastoma tumor size by 70%. Aneuploidy predicted response to olaparib plus irinotecan.
New research is reshaping treatment for some of the deadliest childhood cancers. A first-in-human clinical trial led by Children's National found that a multi-targeted T-cell therapy produced lasting clinical benefit in children and young adults with diffuse intrinsic pontine glioma (DIPG) and relapsed central nervous system tumors, according to findings published in Nature Medicine.
The Phase 1 study evaluated a multi-targeted T-cell therapy designed to strike three proteins commonly found in pediatric brain tumors – WT1, PRAME and Survivin. Investigators said 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. The trial successfully established a feasible manufacturing process, identified a maximum tolerated dose and defined an early safety profile, with some patients remaining disease-free years after treatment.
In a separate preclinical study, researchers from King's College London and McMaster University unveiled a modified CAR-T cell therapy that targets the protein GPNMB, which is found on the surface of both tumor cells and the macrophages that support them. In animal models, 12 out of 13 subjects saw their tumors vanish entirely. The findings, published in Nature, have not yet been tested in humans.
Researchers at RCSI University of Medicine and Health Sciences reported the first preclinical evidence for an mRNA vaccine against neuroblastoma, the deadliest form of childhood cancer. Using targeted peptide nanoparticles designed to recognize Glypican 2 (GPC2), a protein found on the surface of neuroblastoma cells, the vaccine delayed tumour development by between 10 and 11 days and reduced tumour size by approximately 70 percent. The approach builds on the same mRNA technology used in COVID-19 vaccines and could be tailored to individual patients.
In a Phase I/II clinical trial embedded in the AcSé-eSMART study, researchers at the University of Birmingham uncovered a novel biomarker that could predict treatment response in children with Ewing Sarcoma and other solid tumors. The trial enrolled 70 pediatric and young adult participants with relapsed or recurrent tumors and combined the chemotherapy agent irinotecan with the PARP inhibitor olaparib. While the treatment achieved disease stabilization or tumor shrinkage in 12 patients, the anticipated genomic indicators did not predict benefit. Instead, a high aneuploidy score – the presence of an abnormal number of chromosomes – emerged as a highly significant marker, with patients exhibiting high aneuploidy substantially more likely to respond favorably.
A clinical trial at Colorado State University's College of Veterinary Medicine and Biomedical Sciences is testing a combination of CAR T-cell therapy and the oral drug verdinexor in dogs with naturally occurring brain tumors, which are biologically similar to pediatric high-grade glioma. The hypothesis is that verdinexor may alter the tumor microenvironment to make it more permissive for CAR T cells to function. The trial mirrors standard pediatric care: dogs receive upfront radiation therapy, the current standard of care for canine brain tumors, then receive the experimental CAR T-cell therapy afterward.
Meanwhile, UK children with DIPG have been locked out of a potentially life-extending drug trial due to Brexit. Around 30 children in Britain each year are diagnosed with DIPG, an incurable and inoperable tumour that affects the brainstem. The international Biomede trial, which began in 2017, is testing a drug approved in the United States combined with radiotherapy. The second phase of the trial has been approved by European regulators, but it has not been approved in the UK because, under the UK framework, it is being counted as a new trial that needs new approval. Cancer Research UK said Brexit has led to delays in the launch of clinical trials and increased costs for multiple drugs.
A narrative review published in the World Journal of Pediatric Surgery on January 6, 2026, from specialists at the Royal Hospital for Children in Glasgow and the University of Liverpool, brings diagnosis, risk classification, surgery, chemotherapy, immunotherapy, and survivorship for neuroblastoma into a single clinical framework. Neuroblastoma is the most common solid tumor outside the brain in children younger than five years old and accounts for about 15% of pediatric cancer deaths. Five-year survival exceeds 90% for low- and intermediate-risk disease but remains below 60% for high-risk cases.
At UC San Diego and Rady Children's Hospital, researchers are pioneering a novel nanomedicine technology designed to transport anti-cancer drugs at lower doses directly to brain tumor sites. Because the blood-brain barrier blocks more than 98% of small-molecule drugs, innovative delivery strategies are essential. The approach could also apply to breast and lung cancer, which can metastasize to the brain.