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

Human endogenous retroviruses (HERVs) are remnants of ancient viral infections that have been integrated into the human genome over millions of years, now comprising nearly 8% of human DNA (Belshaw et al., 2004). In healthy somatic cells, these sequences are typically silenced through epigenetic mechanisms such as DNA methylation and histone modification (Hurst and Magiorkinis, 2015). However, in many types of cancer, these silencing mechanisms fail, leading to the reactivation and expression of HERV-derived proteins and peptides (Rooney et al., 2015). These expressed products act as tumor-associated antigens (TAAs) because they are absent or highly restricted in normal tissues but prevalent in malignant cells, such as those in melanoma, breast cancer, and renal cell carcinoma (Cherkasova et al., 2016). Therapeutic strategies targeting HERV-derived antigens include monoclonal antibodies, cancer vaccines, and chimeric antigen receptor (CAR) T-cell therapies designed to recognize these viral signatures (Krishnamurthy et al., 2015). By exploiting the unique expression profile of HERVs, these therapies aim to provide high specificity for tumor cells while sparing healthy tissue, potentially overcoming some of the limitations of traditional tumor antigens (Attermann et al., 2018).

Other names

HERV antigenEndogenous retroviral antigenERV-derived tumor antigenHuman endogenous retrovirus protein

Targeting of aberrantly expressed retroviral proteins to induce T-cell mediated cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), or neutralization of pro-inflammatory viral envelopes.