Human endogenous retrovirus E-derived peptide CT-RCC-1 presented by HLA-A*11:01 (CT-RCC-1/HLA-A11)

The CT-RCC-1 HERV-E–derived peptide presented by HLA-A11 is a tumor-specific antigen complex primarily associated with clear cell renal cell carcinoma (ccRCC). This target consists of a specific peptide fragment, derived from the Human Endogenous Retrovirus E (HERV-E) envelope protein, which is presented on the cell surface by the Human Leukocyte Antigen A*11:01 (HLA-A11) molecule (Cherkasova et al., 2011, Blood). In healthy tissues, HERV-E is epigenetically silenced; however, in ccRCC, the loss of the von Hippel-Lindau (VHL) tumor suppressor protein leads to the stabilization of hypoxia-inducible factor 2-alpha (HIF-2α), which transactivates the HERV-E promoter (Takahashi et al., 2008, J. Exp. Med.). This unique expression mechanism makes the CT-RCC-1/HLA-A11 complex a highly selective target for immunotherapy, as it is absent in normal tissues but prevalent in VHL-deficient tumors. Therapeutic approaches targeting this complex involve the use of T-cell receptor (TCR) engineered T cells designed to recognize the pMHC complex and induce targeted lysis of cancer cells (NCT03354390). Because the target is restricted to the HLA-A11 allele, patient selection requires both HLA typing and confirmation of HERV-E expression within the tumor.

Other names

HERV-E-derived RCC antigenHLA-A*11:01-restricted HERV-E peptideCT-RCC-1 peptide-MHC complexASWCISLPL/HLA-A11

T-cell receptor (TCR) binding to the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and tumor cell apoptosis.