CT-RCC HERV-E envelope-derived peptide antigen (CT-RCC HERV-E Env peptide)

The CT-RCC HERV-E envelope-derived peptide antigen originates from transcripts of a novel human endogenous retrovirus type E (HERV-E) provirus located on chromosome 6q, selectively expressed in VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common kidney cancer subtype, but absent in normal kidney tissues or other tumors. This provirus contains long open reading frames in its envelope (env) gene, enabling translation of partial surface (SU) and transmembrane (TM) proteins, from which immunogenic HLA-A*0201-restricted peptides such as CR1, SU1, and TM1 are derived and presented on ccRCC cell surfaces. These peptides stimulate CD8+ T cells in vitro from healthy donors, generating cytotoxic T lymphocytes (CTLs) that specifically recognize and kill HERV-E-expressing, HLA-A*0201-positive ccRCC cells, demonstrating tumor-restricted immunogenicity. Expression is driven by VHL inactivation, leading to HIF stabilization and LTR hypomethylation specific to ccRCC. Preclinical studies show T cells engineered with TCRs against the related CT-RCC-1 HERV-E peptide exhibit antitumor activity in vitro and regress HERV-E-positive ccRCC tumors in mouse models, positioning these antigens as promising targets for T-cell-based immunotherapies like TCR-T cell therapy. No expression occurs in normal tissues, suggesting a favorable therapeutic window without off-tumor effects.

Other names

HERV-E envelope peptideCT-RCC-Env peptideCR1 peptideSU1 peptideTM1 peptide

T-cell receptor (TCR) engineering targeting HERV-E peptides for cytotoxic T lymphocyte (CTL) recognition and tumor cell killing