TY  - JOUR
AU  - Grassl, Niklas
AU  - Poschke, Isabel
AU  - Lindner, Katharina
AU  - Bunse, Lukas
AU  - Mildenberger, Iris
AU  - Boschert, Tamara
AU  - Jähne, Kristine
AU  - Green, Edward W
AU  - Hülsmeyer, Ingrid
AU  - Jünger, Simone
AU  - Kessler, Tobias
AU  - Suwala, Abigail K
AU  - Eisele, Philipp
AU  - Breckwoldt, Michael
AU  - Vajkoczy, Peter
AU  - Grauer, Oliver M
AU  - Herrlinger, Ulrich
AU  - Tonn, Joerg-Christian
AU  - Denk, Monika
AU  - Sahm, Felix
AU  - Bendszus, Martin
AU  - von Deimling, Andreas
AU  - Winkler, Frank
AU  - Wick, Wolfgang
AU  - Platten, Michael
AU  - Sahm, Katharina
TI  - A H3K27M-targeted vaccine in adults with diffuse midline glioma.
JO  - Nature medicine
VL  - 29
IS  - 10
SN  - 1078-8956
CY  - New York, NY
PB  - Nature America Inc.
M1  - DKFZ-2023-01912
SP  - 2586-2592
PY  - 2023
N1  - #EA:D170#LA:D170# / 2023 Oct;29(10):2586-2592 / HI-TRON
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37735561
DO  - DOI:10.1038/s41591-023-02555-6
UR  - https://inrepo02.dkfz.de/record/283125
ER  -