Human epidermal growth factor receptor 2 (HER2) peptide-MHC complex (HER2-pMHC)

Human epidermal growth factor receptor 2 (HER2), also known as ERBB2, is a transmembrane tyrosine kinase receptor that is frequently overexpressed in breast, gastric, and ovarian cancers (UniProt P04626). While conventional therapies like trastuzumab target the surface-exposed protein, an alternative approach involves targeting HER2-derived peptides that are processed intracellularly and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Peoples et al., 2005, JCO). These peptide-MHC complexes act as ligands for specific T-cell receptors (TCRs), enabling the immune system to recognize and eliminate malignant cells. This indirect targeting strategy is primarily utilized in the development of cancer vaccines, such as NeuVax (E75), and TCR-engineered T-cell (TCR-T) therapies (Lowenfeld et al., 2014, OncoImmunology). By focusing on the cellular immune response, these treatments can potentially overcome resistance to antibody-based drugs and target cells with lower levels of HER2 expression. However, the approach requires precise HLA matching and carries risks of on-target off-tumor toxicity, particularly in the heart and lungs where low levels of HER2 are naturally present (Morgan et al., 2010, Molecular Therapy).

Other names

ErbB2 peptide-HLA complexHER2/neu peptide-MHCHLA-presented HER2 peptidesHER2-derived epitope-MHC complex

Induction of T-cell mediated cytotoxicity through the recognition of HER2-derived peptides presented by MHC molecules, leading to the targeted destruction of HER2-expressing cells.