Histone H3.3 K27M peptide-HLA-A*02:01 complex (H3K27M-HLA-A2)

The H3K27M-HLA-A*02:01 complex is a tumor-specific neoantigen found in the majority of diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma (DIPG). It arises from a somatic mutation in the H3F3A or HIST1H3B genes, where lysine 27 is replaced by methionine (H3K27M), leading to the inhibition of Polycomb Repressive Complex 2 (PRC2) and a global loss of H3K27 trimethylation (Chheda et al., 2018; Filbin et al., 2018). This mutation is highly specific to tumor cells, making the H3K27M peptide presented on HLA-A*02:01 an ideal target for precision immunotherapy. Research has focused on developing B-cell receptors (BCRs) and TCR-like antibodies that can specifically recognize this peptide-MHC complex on the cell surface (Okada et al., US20230029244A1). These therapeutic agents aim to induce immune-mediated destruction of glioma cells while sparing healthy brain tissue, which lacks the mutation. However, challenges remain regarding the delivery of these agents across the blood-brain barrier and the potential for neuroinflammatory side effects (Mueller et al., 2019).

Other names

H3K27M neoantigenH3.3K27MH3F3A K27M epitopeH3K27M-HLA complexK27M-mutated histone H3

Targeted immunotherapy utilizing B-cell receptors or TCR-like antibodies to recognize the H3K27M neoepitope presented by HLA-A*02:01, facilitating immune-mediated destruction of mutant glioma cells.