1. K27M-mutant histone-3 as a novel target for glioma immunotherapy.
- Author
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Ochs, Katharina, Ott, Martina, Bunse, Theresa, Sahm, Felix, Bunse, Lukas, Deumelandt, Katrin, Sonner, Jana K., Keil, Melanie, von Deimling, Andreas, Wick, Wolfgang, and Platten, Michael
- Subjects
IMMUNOTHERAPY ,GLIOMAS ,HISTONES - Abstract
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 (H3F3A) 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. [ABSTRACT FROM PUBLISHER]
- Published
- 2017
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