期刊
ONCOIMMUNOLOGY
卷 6, 期 7, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2017.1328340
关键词
Glioma; K27M-mutant histone H3; neoepitope; vaccination
资金
- Medical Faculty, University of Heidelberg
- Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology MD/PhD program, University Heidelberg
- German-Israeli Helmholtz Research School in Cancer Biology
- Helmholtz International Graduate School for Cancer Research at DKFZ
- Stiftung fur Krebs-und Scharlachforschung
- NCT 3.0 program
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.
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