Target intelligence / Profile preview

Histone H3.3 K27M peptide presented on HLA-A*02:01 (H3.3K27M-HLA-A*02:01 peptide)

Target
H3.3K27M-HLA-A*02:01 peptide
Molecular classification
Peptide-MHC complex, Neoantigen, Histone modification-derived neoantigen
01

Overview

The **Histone H3.3 K27M peptide presented on HLA-A*02:01** is a neoantigen complex consisting of a mutant peptide derived from the H3.3 histone variant (with a lysine-to-methionine substitution at position 27), bound by the human leukocyte antigen HLA-A*02:01. This neoantigen is frequently found in diffuse midline glioma (DMG), including pediatric diffuse intrinsic pontine glioma (DIPG), and has been the focus of cancer immunotherapy research, including peptide vaccines and chimeric antigen receptor (CAR) T cell strategies[1][4][5]. While preclinical studies demonstrated binding of the mutant peptide to HLA-A*02:01 and in vitro immune recognition, recent research has shown that the natural presentation level of this peptide-MHC complex on tumor cells is extremely low or undetectable, which limits its practicality as a therapeutic immunotherapy target[2][3]. Nevertheless, it remains under clinical investigation as a model for targeting tumor-specific, mutation-driven neoantigens in cancer.

Other names
H3.3K27M peptide-HLA-A*02:01 complexH3.3K27M neoepitope-HLA-A*02:01H3.3K27M 26–35 peptide bound to HLA-A*02:01
02

Mechanism of action

Induction of CD8⁺ T cell immunity via peptide vaccine targeting the presented neoantigen[4][5]\nRe-direction of cytotoxic T lymphocytes (CTLs) or CAR-T cells to target tumor cells presenting the H3.3K27M peptide-HLA complex[2][3]

03

Biological functions

Antigen presentationImmune recognitionT cell activation (putative/targeted)
04

Disease associations

CancerDiffuse midline glioma (DMG)Pediatric brain tumor
05

Safety considerations

Low antigen density on tumor cells limits effectiveness and could lead to off-target effects if not adequately restricted[2][3]Antigen escape and tumor heterogeneity[3]Potential autoimmunity (in theory, if cross-reactivity with non-tumor tissues)
06

Interacting drugs

H3.3K27M-specific peptide vaccine

3 more in the full profile.

07

Biomarkers

H3.3K27M mutation statusHLA-A*02:01 positivity

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