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Volume 13
Issue 12
10.3390/vaccines13121215
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Peptide Vaccines for Pediatric High-Grade Glioma and Diffuse Midline Glioma: Current Progress and Future Perspectives

by
Aron K. Mebrahtu
1,
Vatsal Jain
2,3,
Eliese M. Moelker
2,3,
Alexandra M. Hoyt-Miggelbrink
2,3,
Katayoun Ayasoufi
2,3,*,† and
Eric M. Thompson
4,*,†
1
School of Medicine, Duke University, Durham, NC 27710, USA
2
Department of Neurosurgery, Duke University, Durham, NC 27710, USA
3
The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC 27710, USA
4
Department of Neurological Surgery, Washington University, St. Louis, MO 63110, USA
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Vaccines 2025, 13(12), 1215; https://doi.org/10.3390/vaccines13121215
Submission received: 31 October 2025 / Revised: 26 November 2025 / Accepted: 26 November 2025 / Published: 30 November 2025
(This article belongs to the Special Issue The Development of Peptide-Based Vaccines)
Versions Notes

Abstract

High-grade gliomas (HGGs) and diffuse midline gliomas (DMGs) in pediatric patients carry a poor prognosis, necessitating the rapid development of novel therapies. Peptide vaccines represent a safe, repeatable, and rational immunotherapeutic modality aimed at inducing potent, tumor-specific T-cell responses. In this review, we define the scope of current progress by arguing that immunogenicity in children with HGG/DMG hinges on three factors: appropriate antigen class (neoantigen vs. TAA), the use of potent immunoadjuvants, and successful navigation of immune suppression. To address the gap between biological promise and clinical reality, we analyze clinical trials targeting shared tumor-associated antigens (e.g., CMV pp65, Survivin) and specific shared neoantigens (H3.3K27M). Crucially, we highlight pivotal data from the PNOC007 trial, where the magnitude of H3.3K27M-specific T-cell expansion correlated directly with significantly longer overall survival (OS), establishing a causal link between pharmacodynamics and clinical benefit. However, the unique challenges of the immunosuppressive tumor microenvironment and the detrimental effect of necessary corticosteroids remain paramount barriers. Future success relies on multi-modal combination strategies, the development of next-generation personalized neoantigen vaccines, and the application of advanced neuroimaging to accurately assess treatment response.
Keywords: pediatric high-grade glioma; diffuse midline glioma (DMG); peptide vaccine; immunotherapy; H3.3K27M; CMV pp65; pseudo progression (PsPD); poly-ICLC; temozolomide pediatric high-grade glioma; diffuse midline glioma (DMG); peptide vaccine; immunotherapy; H3.3K27M; CMV pp65; pseudo progression (PsPD); poly-ICLC; temozolomide

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MDPI and ACS Style

Mebrahtu, A.K.; Jain, V.; Moelker, E.M.; Hoyt-Miggelbrink, A.M.; Ayasoufi, K.; Thompson, E.M. Peptide Vaccines for Pediatric High-Grade Glioma and Diffuse Midline Glioma: Current Progress and Future Perspectives. Vaccines 2025, 13, 1215. https://doi.org/10.3390/vaccines13121215

AMA Style

Mebrahtu AK, Jain V, Moelker EM, Hoyt-Miggelbrink AM, Ayasoufi K, Thompson EM. Peptide Vaccines for Pediatric High-Grade Glioma and Diffuse Midline Glioma: Current Progress and Future Perspectives. Vaccines. 2025; 13(12):1215. https://doi.org/10.3390/vaccines13121215

Chicago/Turabian Style

Mebrahtu, Aron K., Vatsal Jain, Eliese M. Moelker, Alexandra M. Hoyt-Miggelbrink, Katayoun Ayasoufi, and Eric M. Thompson. 2025. "Peptide Vaccines for Pediatric High-Grade Glioma and Diffuse Midline Glioma: Current Progress and Future Perspectives" Vaccines 13, no. 12: 1215. https://doi.org/10.3390/vaccines13121215

APA Style

Mebrahtu, A. K., Jain, V., Moelker, E. M., Hoyt-Miggelbrink, A. M., Ayasoufi, K., & Thompson, E. M. (2025). Peptide Vaccines for Pediatric High-Grade Glioma and Diffuse Midline Glioma: Current Progress and Future Perspectives. Vaccines, 13(12), 1215. https://doi.org/10.3390/vaccines13121215

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