Human endogenous retrovirus type E envelope peptide presented by HLA-A*11:01 (HERV-E/HLA-A*11:01)

The target "CT-RCC-1 HERV-E peptide presented by HLA-A*11:01" is a tumor-specific peptide-MHC complex primarily expressed in clear cell renal cell carcinoma (ccRCC). It consists of a 9-amino acid peptide, ATIGTAMNY, derived from the envelope (env) protein of the Human Endogenous Retrovirus type E (HERV-E), which is presented on the cell surface by the HLA-A*11:01 allele (Takahashi et al., 2008). In healthy tissues, HERV-E is transcriptionally silent due to epigenetic regulation; however, in the majority of ccRCC cases, the loss of the von Hippel-Lindau (VHL) tumor suppressor gene leads to the stabilization of hypoxia-inducible factor 2 alpha (HIF-2α), which directly activates the HERV-E promoter (Cherkasova et al., 2011). This unique mechanism results in highly restricted expression of the antigen in tumor cells, making it an ideal candidate for targeted immunotherapy. Current therapeutic approaches focus on T-cell receptor (TCR) engineered T-cells designed to recognize this specific pMHC complex, with clinical trials (e.g., NCT03354390) investigating their safety and efficacy in patients with metastatic ccRCC. The success of these therapies depends on the patient's HLA-A*11:01 status and the presence of HERV-E mRNA within the tumor (Roszik et al., 2017). While the target is highly specific, potential safety concerns include the theoretical risk of on-target off-tumor toxicity if low-level HERV-E expression exists in vital organs, although such expression has not been significantly documented in humans.

Other names

CT-RCC-1ATIGTAMNY peptideHERV-E env peptideHERV-E-derived antigenCT-RCC antigen

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