Human endogenous retrovirus-derived tumor antigens presented as peptide-major histocompatibility complexes (HERV-pMHC) (HERV-pMHC)

Human endogenous retrovirus (HERV)-derived tumor antigens are peptides originating from ancient retroviral elements that comprise approximately 8% of the human genome (Lander et al., 2001, Nature). While usually silenced by epigenetic mechanisms in healthy cells, these sequences are frequently reactivated in triple-negative breast cancer (TNBC) due to global DNA hypomethylation (Rooney et al., 2015, Cell). Once translated, HERV proteins are processed into peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, forming HERV-pMHC complexes. These complexes are recognized as 'non-self' or 'altered-self' by T cells, making them potent targets for immunotherapy (Wang-Johanning et al., 2012, Cancer Research). Current therapeutic strategies include TCR-engineered T cells and vaccines designed to elicit a robust cytotoxic T-cell response against TNBC cells expressing these specific viral remnants (Saini et al., 2020, Science Immunology). Because HERV expression is highly restricted to malignant tissues, these pMHC complexes offer a high degree of tumor specificity, potentially reducing the risk of systemic toxicity compared to traditional chemotherapy. However, the effectiveness of these therapies depends on the stable expression of MHC molecules and the specific HLA alleles of the patient (Garrido et al., 2016, Cancer Immunology, Immunotherapy).

Other names

HERV-derived neoantigensHERV-derived tumor-specific antigensHERV-derived tumor-associated antigensEndogenous retroviral pMHC

Targeted recognition of HERV-derived peptides in the context of MHC molecules by engineered T-cell receptors or antibodies, inducing cytotoxic T-lymphocyte mediated apoptosis of tumor cells.