A H3K27M-targeted vaccine in adults with diffuse midline glioma.
Niklas GrasslIsabel C PoschkeKatharina A M LindnerLukas BunseIris MildenbergerTamara BoschertKristine JähneEdward W GreenIngrid HülsmeyerSimone JüngerTobias KesslerAbigail K SuwalaPhilipp EiseleMichael O BreckwoldtPeter VajkoczyOliver M GrauerUlrich HerrlingerJoerg-Christian TonnMonika DenkFelix SahmMartin BendszusAndreas von DeimlingFrank WinklerWolfgang WickMichael PlattenKatharina SahmPublished in: Nature medicine (2023)
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.
Keyphrases
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