Human endogenous retrovirus-derived peptide–human leukocyte antigen complex (HERV-peptide–HLA complex)

Human endogenous retrovirus (HERV)-derived peptide–HLA complexes are a class of tumor-specific antigens that arise from the reactivation of ancient viral sequences integrated into the human genome. While these retroviral elements are typically silenced in healthy adult tissues through epigenetic mechanisms, they are frequently expressed in ovarian cancer cells, where they are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (PMID: 25635322, 30104631). These complexes serve as highly specific targets for immunotherapy because they are largely absent from the normal proteome, potentially minimizing the risk of central tolerance and off-target effects (PMID: 33500253). Current therapeutic development focuses on T-cell receptor (TCR)-engineered T cells and TCR-like antibodies designed to recognize specific HERV-K or HERV-E epitopes in the context of common HLA alleles like HLA-A*02:01 (PMID: 29463573). The efficacy of these treatments depends on the stable surface expression of the peptide-MHC complex and the patient's specific HLA haplotype.

Other names

HERV-derived tumor-associated antigenHERV-derived neoantigenEndogenous retrovirus-derived peptide-MHC complexHERV-K-derived peptide-HLA complexHERV-E-derived peptide-HLA complexHERV-K (HML-2) antigen

Therapeutic agents targeting these complexes utilize T-cell receptors (TCRs) or TCR-like antibodies to specifically recognize the combination of a HERV-derived peptide bound within the groove of an HLA molecule, triggering T-cell mediated cytotoxicity or antibody-dependent cellular cytotoxicity (ADCC) against the tumor cell.