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A H3K27M-targeted vaccine in adults with diffuse midline glioma

Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype of diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses that control H3K27M+ tumors in major histocompatibility comp...

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Hauptverfasser: Graßl, Niklas (VerfasserIn) , Poschke, Isabel (VerfasserIn) , Lindner, Katharina (VerfasserIn) , Bunse, Lukas (VerfasserIn) , Mildenberger, Iris (VerfasserIn) , Boschert, Tamara (VerfasserIn) , Jähne, Kristine (VerfasserIn) , Green, Edward W. (VerfasserIn) , Hülsmeyer, Ingrid (VerfasserIn) , Jünger, Simone (VerfasserIn) , Keßler, Tobias (VerfasserIn) , Suwala, Abigail Kora (VerfasserIn) , Eisele, Philipp (VerfasserIn) , Breckwoldt, Michael O. (VerfasserIn) , Vajkoczy, Peter (VerfasserIn) , Grauer, Oliver M. (VerfasserIn) , Herrlinger, Ulrich (VerfasserIn) , Tonn, Joerg-Christian (VerfasserIn) , Denk, Monika (VerfasserIn) , Sahm, Felix (VerfasserIn) , Bendszus, Martin (VerfasserIn) , Deimling, Andreas von (VerfasserIn) , Winkler, Frank (VerfasserIn) , Wick, Wolfgang (VerfasserIn) , Platten, Michael (VerfasserIn) , Sahm, Katharina (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 21 September 2023
In: Nature medicine
Year: 2023, Jahrgang: 29, Heft: 10, Pages: 2586-2592
ISSN:1546-170X
DOI:10.1038/s41591-023-02555-6
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41591-023-02555-6
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41591-023-02555-6
Volltext
Verfasserangaben:Niklas Grassl, Isabel Poschke, Katharina Lindner, Lukas Bunse, Iris Mildenberger, Tamara Boschert, Kristine Jähne, Edward W. Green, Ingrid Hülsmeyer, Simone Jünger, Tobias Kessler, Abigail K. Suwala, Philipp Eisele, Michael O. Breckwoldt, Peter Vajkoczy, Oliver M. Grauer, Ulrich Herrlinger, Joerg-Christian Tonn, Monika Denk, Felix Sahm, Martin Bendszus, Andreas von Deimling, Frank Winkler, Wolfgang Wick, Michael Platten, Katharina Sahm
Beschreibung
Zusammenfassung:Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype of diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses that control H3K27M+ tumors in major histocompatibility complex-humanized mice. Here we describe a first-in-human treatment with H3K27M-vac of eight adult patients with progressive H3K27M+ diffuse midline glioma on a compassionate use basis. Five patients received H3K27M-vac combined with anti-PD-1 treatment based on physician’s discretion. Repeat vaccinations with H3K27M-vac were safe and induced CD4+ T cell-dominated, mutation-specific immune responses in five of eight patients across multiple human leukocyte antigen types. Median progression-free survival after vaccination was 6.2 months and median overall survival was 12.8 months. One patient with a strong mutation-specific T cell response after H3K27M-vac showed pseudoprogression followed by sustained complete remission for >31 months. Our data demonstrate safety and immunogenicity of H3K27M-vac in patients with progressive H3K27M+ diffuse midline glioma.
Beschreibung:Gesehen am 28.09.2023
Beschreibung:Online Resource
ISSN:1546-170X
DOI:10.1038/s41591-023-02555-6

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