Human endogenous retrovirus type E peptide CT-RCC-1 (CT-RCC-1)

Human endogenous retrovirus type E peptide CT-RCC-1 is a 10-mer peptide with the sequence ATFLGSLTWK, derived from the envelope gene of a specific human endogenous retrovirus (HERV-E) located on chromosome 6q (Takahashi et al., J. Clin. Invest. 2008; Cherkasova et al., Cancer Res. 2016). This peptide is selectively expressed in clear cell renal cell carcinoma (ccRCC) as a result of epigenetic dysregulation, specifically the inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene, which leads to the stabilization of hypoxia-inducible factors (HIF) that drive HERV-E transcription (Nadal et al., J. Clin. Oncol. 2024; Chen et al., ASCO 2024). Because HERV-E is typically silenced in normal tissues, CT-RCC-1 acts as a highly specific tumor-associated antigen (TAA) (NCI Drug Dictionary). It is presented on the surface of cancer cells by the HLA-A*11:01 major histocompatibility complex (MHC) (Barisic et al., AACR 2021). Therapeutic development focuses on adoptive T-cell therapy, where a patient's T cells are engineered to express a T-cell receptor (TCR) that specifically recognizes the CT-RCC-1/HLA-A11 complex (NCT03354390). Clinical trials have demonstrated that these TCR-T cells can traffic to tumor sites and induce regression in patients with metastatic ccRCC, though challenges remain regarding in vivo persistence and efficacy (Nadal et al., ASCO 2023).

Other names

CT-RCC-1 antigenHERV-E-derived peptideATFLGSLTWKHERV-E peptideCT-RCC1

T-cell receptor (TCR) mediated recognition of the CT-RCC-1 peptide presented by HLA-A*11:01 on tumor cells, leading to cytotoxic T-lymphocyte (CTL) activation and tumor cell lysis.