Human endogenous retrovirus E-derived peptide-HLA complex (HERV-E-HLA)

The HERV-E–derived peptide presented by HLA on tumor cells is a highly specific tumor-associated antigen complex primarily identified in clear cell renal cell carcinoma (ccRCC). Human endogenous retroviruses (HERVs) are remnants of ancient viral infections integrated into the human genome that are typically silenced in normal adult tissues through epigenetic mechanisms (Takahashi et al., 2008, J Exp Med). In ccRCC, the loss of the von Hippel-Lindau (VHL) tumor suppressor gene leads to the stabilization of hypoxia-inducible factors (HIF), which triggers the aberrant expression of HERV-E (Cherkasova et al., 2011, Cancer Res). A specific 9-amino acid peptide derived from the HERV-E envelope protein is processed and presented on the cell surface by HLA-A*02:01 molecules. Because this expression is highly restricted to VHL-deficient tumor cells and absent in healthy tissues, the HERV-E-HLA complex serves as an ideal target for T-cell receptor (TCR) engineered T-cell therapies. Clinical investigations have shown that T cells targeting this complex can induce significant tumor regression in patients with metastatic ccRCC (NCT03354390).

Other names

HERV-E antigenCT-RCC antigenHERV-E-derived renal cell carcinoma antigenHERV-E envelope peptideHERV-E-derived peptide presented by HLA-A*02:01

Engineered T-cell receptors (TCRs) specifically bind to the HERV-E peptide-HLA-A*02:01 complex on the surface of tumor cells, triggering T-cell activation, cytokine release, and direct cytotoxic lysis of the target cell.