K27M-mutant histone-3 as a novel target for glioma immunotherapy.

Mutation-specific vaccines have become increasingly important in glioma immunotherapy; however， shared neoepitopes are rare. For diffuse gliomas， a driver mutation in the gene for isocitrate dehydrogenase type-1 has been shown to produce an immunogenic epitope currently targeted in clinical trials. For highly aggressive midline gliomas， a recurrent point mutation in the histone-3 gene () causes an amino acid change from lysine to methionine at position 27 (K27M). Here， we demonstrate that a peptide vaccine against K27M-mutant histone-3 is capable of inducing effective， mutation-specific， cytotoxic T-cell- and T-helper-1-cell-mediated immune responses in a major histocompatibility complex (MHC)-humanized mouse model. By proving an immunologically effective presentation of the driver mutation H3K27M on MHC class II in human H3K27M-mutant gliomas， our data provide a basis for the further clinical development of vaccine-based or cell-based immunotherapeutic approaches targeting H3K27M.