K27M-mutant histone-3 as a novel target for glioma immunotherapy. (3rd July 2017)

• Record Type: Journal Article
• Authors: Ochs, Katharina; Ott, Martina; Bunse, Theresa; Sahm, Felix; Bunse, Lukas; Deumelandt, Katrin; Sonner, Jana K.; Keil, Melanie; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael
• Is Part Of: Oncoimmunology. Volume 6:Number 7(2017)
• Publication Date: 2017-07-03
• Subjects: Glioma -- K27M-mutant histone H3 -- neoepitope -- vaccination; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1328340
• Languages: English
• ISSNs: 2162-402X

Abstract

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.