Human endogenous retrovirus-derived neoantigen (HERV-neoantigen)

Human endogenous retrovirus (HERV)-derived neoantigens are a novel class of tumor-specific targets originating from ancient viral sequences integrated into the human genome. Although these elements are typically silenced in healthy tissues through epigenetic regulation, they can be reactivated in various malignancies, including melanoma, renal cell carcinoma, and glioblastoma, due to the loss of epigenetic control. Once expressed, these viral-derived proteins are processed into peptides and presented on the cell surface by patient-specific Major Histocompatibility Complex (MHC) molecules, where they can be recognized by the immune system as non-self antigens. This makes them particularly valuable for immunotherapy in cold tumors with low mutational burden, where traditional mutation-derived neoantigens are scarce. Therapeutic strategies involve the use of personalized cancer vaccines, such as those developed by Evaxion Biotech, or the administration of epigenetic modifiers like decitabine to induce viral mimicry and enhance antigen presentation. By targeting these shared yet tumor-specific sequences, clinicians aim to broaden the reach of immunotherapy to a wider range of cancer patients.

Other names

Endogenous retrovirus-derived neoantigenERV-derived neoantigenEVE-derived neoantigenDark genome antigenHERV-derived tumor-associated antigenEndogenous retroviral element-derived neoantigen

Induction of T-cell mediated cytotoxicity through the recognition of viral-derived peptides presented on MHC molecules; epigenetic induction of antigen expression (viral mimicry) to enhance tumor immunogenicity.