Mutant ERBB2-derived neoantigen peptides presented by Human Leukocyte Antigen (HLA) (Mutant ERBB2-HLA complex)

Mutant ERBB2-derived neoantigens are peptides resulting from somatic mutations in the ERBB2 (HER2) gene that are processed and presented on the surface of cancer cells by Human Leukocyte Antigen (HLA) molecules (1.1.3, 2.3.2). These mutations, such as S310F, L755S, and V777L, create novel amino acid sequences that are absent in normal tissues, making them highly specific targets for the immune system (2.1.1, 2.3.1). Unlike wild-type HER2, which is often overexpressed in various cancers but also present in healthy tissues, these mutant neoantigens allow for the development of therapies that can selectively eliminate tumor cells while sparing normal ones (1.1.3, 1.4.5). Therapeutic strategies targeting these complexes include T-cell receptor-engineered T-cell (TCR-T) therapy and personalized cancer vaccines (1.4.1, 2.4.2). Clinical proof-of-concept has been demonstrated in cases where adoptive transfer of T cells specific for ERBB2-related mutations led to significant tumor regression in patients with metastatic epithelial cancers (1.2.1, 1.4.1). However, the effectiveness of these therapies is limited by the requirement for specific HLA alleles (HLA restriction) and the potential for tumor escape through the loss of HLA expression or the target mutation (1.1.3, 1.4.4).

Other names

HER2 mutant neoantigenERBB2 mutation-derived neoantigenMutant HER2 peptide-MHC complexERBB2 neoepitopeHER2 neoantigen-HLA complexMutant ERBB2-derived neoantigen peptides presented by MHC

T-cell receptor (TCR) binding to the mutant peptide-HLA complex, leading to T-cell activation, cytokine release (e.g., IFN-gamma), and cytotoxic killing of tumor cells.