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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....

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Main Authors: Sahm, Katharina (Author) , Ott, Martina (Author) , Bunse, Theresa (Author) , Sahm, Felix (Author) , Bunse, Lukas (Author) , Deumelandt, Katrin (Author) , Sonner, Jana K. (Author) , Keil, Melanie (Author) , Deimling, Andreas von (Author) , Wick, Wolfgang (Author) , Platten, Michael (Author)
Format: Article (Journal)
Language:English
Published: 05 Jul 2017
In: OncoImmunology
Year: 2017, Volume: 6, Issue: 7
ISSN:2162-402X
DOI:10.1080/2162402X.2017.1328340
Online Access:Verlag, Volltext: http://dx.doi.org/10.1080/2162402X.2017.1328340
Verlag, Volltext: https://doi.org/10.1080/2162402X.2017.1328340
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Author Notes:Katharina Ochs, Martina Ott, Theresa Bunse, Felix Sahm, Lukas Bunse, Katrin Deumelandt, Jana K. Sonner, Melanie Keil, Andreas von Deimling, Wolfgang Wick, Michael Platten
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Summary: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.
Item Description:Gesehen am 25.04.2018
Physical Description:Online Resource
ISSN:2162-402X
DOI:10.1080/2162402X.2017.1328340

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