Human endogenous retrovirus-derived epitopes (HERV epitopes) (HERV epitopes)

Human endogenous retrovirus (HERV)-derived epitopes are peptide fragments originating from ancient viral sequences integrated into the human genome, which are presented on the cell surface by Human Leukocyte Antigen (HLA) class I or II molecules (Cherkasova et al., 2013, J Clin Invest). While these sequences are typically transcriptionally silenced in healthy adult tissues through epigenetic mechanisms, they can become reactivated and overexpressed in various pathological states, particularly in malignancies such as renal cell carcinoma, melanoma, and breast cancer (Saini et al., 2020, Sci Adv; Rooney et al., 2015, Cell). Once expressed and processed, these HERV-derived peptides function as tumor-associated or tumor-specific antigens that can be recognized by the T-cell receptor (TCR) of CD8+ or CD4+ T cells (Takahashi et al., 2008, J Immunother). This recognition triggers a targeted immune response, leading to the destruction of the HERV-expressing cells. Consequently, HERV-derived epitopes have emerged as promising targets for cancer immunotherapies, including TCR-engineered T-cell (TCR-T) therapies and therapeutic vaccines (Mullins et al., 2003, J Mamm Gland Biol Neoplasia). The high specificity of certain HERV expressions to tumor cells potentially minimizes the risk of off-target effects, although thorough screening for low-level expression in vital organs remains a critical safety consideration for clinical development.

Other names

HERV antigensHuman endogenous retrovirus antigensHERV-derived peptidesHERV-HLA complexesHERV-TCR targetsHERV-E antigensHERV-K antigens

T-cell mediated cytotoxicity following TCR recognition of the HERV-peptide-HLA complex