Human endogenous retrovirus-derived tumor antigen (HERV-TA) (HERV-TA)

Human endogenous retrovirus-derived tumor antigens (HERV-TAs) are a class of shared neoantigens arising from the aberrant expression of ancient viral sequences integrated into the human genome (Riggs et al., 2020). While these sequences are typically silenced in healthy somatic tissues through epigenetic mechanisms like DNA methylation, they become transcriptionally active in triple-negative breast cancer (TNBC) due to widespread DNA hypomethylation (Rooney et al., 2015). Once expressed, HERV-derived proteins are processed by the proteasome and presented as peptides on MHC class I molecules, making them visible to the cellular immune system (Smith et al., 2018). These antigens are particularly attractive for immunotherapy because they are highly tumor-specific and shared across many patients, unlike patient-specific somatic neoantigens (Riggs et al., 2020). Research has identified specific HERV families, such as HERV-K and HERV-H, that produce immunogenic peptides capable of eliciting robust CD8+ T-cell responses in TNBC patients (Riggs et al., 2020). Therapeutic strategies currently under investigation include TCR-engineered T-cell therapies and therapeutic vaccines designed to target these shared viral-like sequences (Smith et al., 2018). Furthermore, the expression of HERV-TAs can be pharmacologically induced or enhanced using DNA methyltransferase inhibitors, a strategy known as viral mimicry that sensitizes tumors to immune checkpoint blockade (Panda et al., 2018).

Other names

HERV-derived neoantigenHERV-derived peptideEndogenous retroviral antigenHERV-K antigenHERV-H antigenHERV-W antigen

T-cell mediated cytotoxicity via recognition of MHC-I restricted HERV peptides; induction of viral mimicry through epigenetic modulation (Riggs et al., 2020; Panda et al., 2018).