Therapeutic cancer vaccination for relapsed and refractory pediatric brain tumors

Knaup Lisa; Eyrich Matthias

doi:10.70401/acrt.2026.0045

Therapeutic cancer vaccination for relapsed and refractory pediatric brain tumors

Lisa Knaup

Matthias Eyrich

*Correspondence to: Matthias Eyrich, Division of Paediatric Haemato-Oncology, Stem Cell Transplantation and Cellular Therapy, Department of Paediatrics, University Hospital Würzburg, Würzburg 97080, Germany. E-mail: eyrich_m@ukw.de

Ageing Cancer Res Treat. 2027;4:202602. 10.70401/acrt.2026.0045

Received: January 10, 2026Accepted: October 28, 2026Published: October 29, 2026

This article belongs to the Special lssue Frontiers in Therapeutic Cancer Vaccination

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Relapsed and refractory paediatric brain tumors—including high-grade gliomas (HGG) such as diffuse hemispheric glioma, diffuse midline glioma (DMG), diffuse intrinsic pontine glioma (DIPG), and atypical teratoid rhabdoid tumors (AT/RT), medulloblastoma (MB) and ependymoma (EPN)—remain among the most treatment-resistant childhood malignancies. Despite multimodal therapy combining maximal safe resection, radiotherapy, and chemotherapy, long-term survival after relapse is exceedingly rare. The limitations of conventional cytotoxic regimens and the largely immune-silent nature of these tumors have driven interest in therapeutic vaccination as a strategy to induce durable, antigen-specific immune responses. Advances in molecular profiling and immunopeptidomics have enabled the identification of tumor-exclusive peptides, even within the low-mutational landscape typical of paediatric gliomas. Preclinical investigations demonstrate that dendritic-cell- (DC), peptide-, or mRNA-based vaccines can elicit tumor-specific cytotoxic T-cell responses and modify the tumor microenvironment. Early clinical experiences in relapsed paediatric HGG and DMG indicate safety and feasibility, with emerging evidence of immune activation and prolongation of survival. Features of paediatric immunity render children particularly responsive to cancer vaccines and insights from paediatric trials may prove valuable for the design of immunotherapeutic strategies in aging-related cancers. This review summarizes current preclinical and clinical developments in paediatric brain-tumor vaccination, focusing on antigen discovery, immunologic mechanisms, vaccine platforms, and translational challenges that define this evolving frontier in paediatric neuro-oncology.

Keywords

Paediatric brain tumors, therapeutic vaccination, immunopeptidomics, dendritic cells, mRNA vaccine, high-grade glioma

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Knaup L, Eyrich M. Therapeutic cancer vaccination for relapsed and refractory pediatric brain tumors. Ageing Cancer Res Treat. 2027;4:202602. https://doi.org/10.70401/acrt.2026.0045