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

TY - JOUR

T1 - K27M-mutant histone-3 as a novel target for glioma immunotherapy

AU - Ochs, Katharina

AU - Ott, Martina

AU - Bunse, Theresa

AU - Sahm, Felix

AU - Bunse, Lukas

AU - Deumelandt, Katrin

AU - Sonner, Jana K

AU - Keil, Melanie

AU - von Deimling, Andreas

AU - Wick, Wolfgang

AU - Platten, Michael

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1080/2162402X.2017.1328340

DO - 10.1080/2162402X.2017.1328340

M3 - SCORING: Journal article

C2 - 28811969

VL - 6

SP - e1328340

JO - ONCOIMMUNOLOGY

JF - ONCOIMMUNOLOGY

SN - 2162-402X

IS - 7

ER -