Human epidermal growth factor receptor 2 (HER2)-derived peptide-HLA complex (HER2-HLA complex)

The Human epidermal growth factor receptor 2 (HER2)-derived peptide-HLA complex consists of short peptide fragments of the HER2 protein presented on the cell surface by Human Leukocyte Antigen (HLA) molecules. This complex serves as a critical target for the cellular immune system, as it is specifically recognized by T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes and CD4+ helper T cells. In many cancers, such as breast, gastric, and ovarian cancer, HER2 is overexpressed, leading to an increased density of these peptide-HLA complexes on the tumor cell surface. Therapeutic strategies targeting this complex include peptide-based vaccines like Nelipepimut-S (E75) and GP2, which aim to prime the patient's immune system to recognize and destroy HER2-positive cells. Additionally, advanced modalities such as TCR-engineered T-cell (TCR-T) therapies and TCR-like antibodies are being developed to directly bind these complexes with high specificity. A significant challenge in targeting this complex is HLA restriction, which limits the applicability of specific treatments to patients with compatible HLA genotypes, such as HLA-A*02:01.

Other names

HER2/neu peptide-MHC complexERBB2 peptide-HLA complexHLA-presented HER2 epitopesHER2-pMHCHER2-derived peptide-HLA-A*02:01 complex

Induction of T-cell mediated cytotoxicity through active immunization or direct targeting of the peptide-HLA complex to trigger an antigen-specific immune response against HER2-expressing tumor cells.