Human Endogenous Retrovirus-derived peptide-Human Leukocyte Antigen complex (HERV-pHLA)

Human Endogenous Retrovirus (HERV)-derived peptide-HLA complexes are specialized molecular targets formed when fragments of reactivated endogenous retroviral proteins are presented on the surface of ovarian cancer cells by Human Leukocyte Antigen (HLA) molecules (Rycaj et al., 2015). While HERVs constitute approximately 8% of the human genome, they are typically transcriptionally silent in healthy tissues but become highly expressed in various malignancies, including ovarian cancer, due to epigenetic changes (Wang-Johanning et al., 2007). These complexes function as tumor-associated antigens (TAAs) that can be recognized by the cellular immune system, specifically by CD8+ T cells via their T-cell receptors (TCRs). In the context of ovarian cancer, specific HERV families such as HERV-K (HML-2) and HERV-W have been identified as being presented by common HLA alleles like HLA-A*02:01 (Saini et al., 2020). Therapeutic interventions targeting these complexes include TCR-engineered T-cell (TCR-T) therapies, TCR-like monoclonal antibodies, and therapeutic vaccines designed to elicit a robust cytotoxic T-lymphocyte response against the tumor (Schiavetti et al., 2002). Because these antigens are minimally expressed in normal tissues, they offer a high degree of tumor specificity, though challenges such as HLA downregulation and potential cross-reactivity with self-peptides remain significant considerations in drug development (PubMed: 32853434).

Other names

HERV-K peptide-HLA complexHERV-W peptide-HLA complexHERV-derived tumor-associated antigensEndogenous retrovirus-derived neoantigensHERV-E peptide-HLA complex

Recognition of the specific peptide-HLA complex by T-cell receptors (TCRs) or TCR-like molecules, leading to T-cell activation and targeted lysis of the cancer cell via perforin and granzyme release.