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

The HERV-E–derived CT-RCC-1 peptide presented by HLA-A*11:01 is a tumor-specific antigen complex primarily expressed in clear cell renal cell carcinoma (ccRCC) (Takahashi et al., 2008). It originates from the reactivation of a human endogenous retrovirus (HERV-E) provirus, a process triggered by the loss of the von Hippel-Lindau (VHL) tumor suppressor gene (Cherkasova et al., 2011). In VHL-deficient cells, the stabilization of hypoxia-inducible factor 2-alpha (HIF-2α) drives the transcription of HERV-E, which is otherwise silenced in normal tissues (Takahashi et al., 2008). The specific peptide CT-RCC-1, with the amino acid sequence ATVFPGEPSL, is processed and presented on the cell surface by the HLA-A*11:01 major histocompatibility complex (MHC) class I molecule (Takahashi et al., 2008). This complex is a key target for cancer immunotherapy, particularly for the development of T-cell receptor (TCR) engineered T-cell therapies (Harari et al., 2017). Because of its restricted expression to tumor cells, targeting this pMHC complex offers a high degree of therapeutic index with minimal off-target effects on healthy tissues (Cherkasova et al., 2016). Clinical strategies focusing on this target involve the adoptive transfer of T cells modified to express TCRs with high affinity for the CT-RCC-1/HLA-A*11:01 complex (Takahashi et al., 2008).

Other names

CT-RCC-1 peptideATVFPGEPSL peptideHLA-A*11:01-restricted HERV-E antigenHERV-E-derived antigen CT-RCC-1

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte (CTL) activation and tumor cell lysis.