%0 Journal Article
%A Grassl, Niklas
%A Poschke, Isabel
%A Lindner, Katharina
%A Bunse, Lukas
%A Mildenberger, Iris
%A Boschert, Tamara
%A Jähne, Kristine
%A Green, Edward W
%A Hülsmeyer, Ingrid
%A Jünger, Simone
%A Kessler, Tobias
%A Suwala, Abigail K
%A Eisele, Philipp
%A Breckwoldt, Michael
%A Vajkoczy, Peter
%A Grauer, Oliver M
%A Herrlinger, Ulrich
%A Tonn, Joerg-Christian
%A Denk, Monika
%A Sahm, Felix
%A Bendszus, Martin
%A von Deimling, Andreas
%A Winkler, Frank
%A Wick, Wolfgang
%A Platten, Michael
%A Sahm, Katharina
%T A H3K27M-targeted vaccine in adults with diffuse midline glioma.
%J Nature medicine
%V 29
%N 10
%@ 1078-8956
%C New York, NY
%I Nature America Inc.
%M DKFZ-2023-01912
%P 2586-2592
%D 2023
%Z #EA:D170#LA:D170# / 2023 Oct;29(10):2586-2592 / HI-TRON
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37735561
%R 10.1038/s41591-023-02555-6
%U https://inrepo02.dkfz.de/record/283125