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

Human endogenous retrovirus type E (HERV-E) CT-RCC-1 is a tumor-specific antigen peptide derived from the expression of an endogenous retrovirus in clear cell renal cell carcinoma (ccRCC) [1, 2]. In normal tissues, this retroviral element is transcriptionally silent; however, in ccRCC, the loss of the von Hippel-Lindau (VHL) tumor suppressor leads to the stabilization of hypoxia-inducible factor 2-alpha (HIF-2α), which transactivates the HERV-E promoter [1, 5]. The CT-RCC-1 peptide, with the amino acid sequence ATFLGSLTWK, is presented on the cell surface by the HLA-A*11:01 molecule [2, 3]. This unique expression pattern makes it an ideal target for immunotherapy, as it is not found in healthy tissues [1, 4]. Therapeutic approaches primarily focus on adoptive cell transfer using T cells engineered with a T-cell receptor (TCR) specific for the CT-RCC-1/HLA-A*11:01 complex [3, 5]. Clinical investigations, such as phase I trials (e.g., NCT03354390), have evaluated the safety and efficacy of these TCR-T cells in patients with metastatic kidney cancer [3, 4]. While the target is highly specific, challenges include the requirement for specific HLA alleles and the need to improve the persistence of engineered T cells in the tumor microenvironment [3, 5].

Other names

HERV-E CT-RCC-1CT-RCC-1 antigenATFLGSLTWK peptideCT-RCC HERV-E peptideHuman endogenous retrovirus type E envelope-derived peptide

T-cell receptor-engineered T-cell therapy (TCR-T) that recognizes the CT-RCC-1 peptide presented by HLA-A*11:01 on the surface of tumor cells, leading to targeted cytotoxicity.