Human leukocyte antigen class II presenting histone H3 K27M-derived epitope (HLA-II/H3K27M)

The target consists of Human Leukocyte Antigen (HLA) class II molecules presenting a neoantigenic peptide derived from the histone H3 K27M mutation. This mutation, a lysine-to-methionine substitution at position 27 of histone H3.3 or H3.1, is a hallmark of diffuse midline gliomas (DMGs), occurring in over 80% of cases (Ochs et al., 2017, Cancer Cell). The HLA-II/H3K27M complex is specifically recognized by CD4+ T cells, which play a crucial role in orchestrating the anti-tumor immune response (Chheda et al., 2018, Nature). Therapeutic interventions targeting this complex include peptide vaccines, such as the H3K27M long peptide vaccine tested in clinical trials (NCT02960230), and TCR-engineered T-cell therapies (Mueller et al., 2020, Journal of Clinical Oncology). Because the mutation is absent in normal tissues, the complex serves as a highly specific target for immunotherapy, aiming to overcome the immunosuppressive environment of the central nervous system. Monitoring for HLA-DRB1*01:01 expression is often required as it is a common allele capable of presenting the immunodominant H3K27M epitope. This target represents a significant advancement in precision oncology for pediatric brain tumors with limited treatment options.

Other names

HLA-DR/H3K27M complexMHC class II-restricted H3K27M epitopeH3.3K27M-HLA-II complexHistone H3 K27M-HLA class II complex

Induction of CD4+ T-cell mediated anti-tumor immunity through the recognition of the mutant histone H3 K27M epitope presented on HLA class II molecules (Ochs et al., 2017).