New York esophageal squamous cell carcinoma 1 (NY-ESO-1) epitopes presented by HLA-B*07, HLA-B*18, and HLA-C*03 (NY-ESO-1/HLA-B*07/B*18/C*03)

New York esophageal squamous cell carcinoma 1 (NY-ESO-1), encoded by the CTAG1B gene, is a prominent cancer-testis antigen (CTA) characterized by its high immunogenicity and restricted expression in normal tissues, primarily the testis and placenta (Chen et al., 1997). This target specifically refers to NY-ESO-1 derived peptide epitopes presented on the cell surface by Human Leukocyte Antigen (HLA) alleles HLA-B*07, HLA-B*18, and HLA-C*03. These peptide-MHC complexes are recognized by CD8+ T-cells, making them critical targets for adoptive cell therapies such as TCR-engineered T-cells (Gnjatic et al., 2006). Specific epitopes include NY-ESO-1 60-72 (APRGPHGGAASGL) for HLA-B*07:02, NY-ESO-1 139-147 (ASGPGGGAPR) for HLA-B*18, and NY-ESO-1 92-100 (LAMPFATPM) for HLA-C*03 (Gnjatic et al., 2000; Gnjatic et al., 2003; Jäger et al., 1998). In oncology, the aberrant expression of NY-ESO-1 in tumors like melanoma and synovial sarcoma allows these HLA-restricted complexes to serve as precise markers for therapeutic intervention. While much clinical development has focused on HLA-A*02 restricted epitopes, targeting epitopes presented by HLA-B*07, HLA-B*18, and HLA-C*03 significantly expands the eligible patient population for TCR-T therapies. Drugs interacting with this target are primarily engineered T-cells designed to bind these specific pMHC complexes with high affinity, triggering a potent cytotoxic immune response. Safety considerations for these therapies include managing systemic inflammatory responses like cytokine release syndrome and ensuring no cross-reactivity with similar peptides in healthy tissues.

Other names

CTAG1BCancer/testis antigen 1BLAGE-2NY-ESO-1 peptide-MHC complexNY-ESO-1/HLA-B7NY-ESO-1/HLA-B18NY-ESO-1/HLA-Cw3

Engineered T-cell receptors (TCRs) recognize specific NY-ESO-1 peptides presented by HLA-B*07, HLA-B*18, or HLA-C*03 molecules on the surface of tumor cells, leading to T-cell activation, the release of cytotoxic granules (perforin/granzyme), and pro-inflammatory cytokine production, which results in targeted tumor cell lysis.