New York esophageal squamous cell carcinoma 1 (NY-ESO-1) peptide–HLA class I complex (NY-ESO-1/HLA complex)

The New York esophageal squamous cell carcinoma 1 (NY-ESO-1) peptide–HLA class I complex is a molecular target consisting of a peptide fragment from the NY-ESO-1 protein presented by the Human Leukocyte Antigen (HLA) system, typically HLA-A*02:01 (UniProt P14136; PMID: 30103321). NY-ESO-1 is a cancer-testis antigen encoded by the CTAG1B gene, characterized by high expression in various malignancies such as synovial sarcoma and melanoma, while being restricted to germ cells in healthy tissues (PMID: 34253456). This restricted expression profile makes the NY-ESO-1/HLA complex an ideal target for T-cell receptor (TCR) engineered T-cell therapies (TCR-T). These therapies utilize patient-derived T cells modified to express a high-affinity TCR that specifically recognizes the NY-ESO-1 peptide (often the SLLMWITQC epitope), triggering a cytotoxic immune response against the tumor (PMID: 29301824, PMID: 38537575). Upon recognition of the complex, the engineered CD8+ T cells proliferate and release cytotoxic granules and pro-inflammatory cytokines to induce apoptosis in the target cancer cells. In 2024, afamitresgene autoleucel became the first FDA-approved TCR-T therapy targeting this complex for the treatment of advanced synovial sarcoma, representing a major advancement in solid tumor immunotherapy (FDA.gov, 2024).

Other names

CTAG1B/HLA-A*02:01 complexNY-ESO-1/MHC class I complexSLLMWITQC-HLA-A*02:01NY-ESO-1–specific CD8+ T-cell receptor targetCancer-testis antigen 1B/HLA complex

T-cell receptor (TCR) engineered T-cell therapy involves modifying autologous T cells to express a specific TCR that recognizes the NY-ESO-1 peptide presented by HLA class I molecules, leading to targeted tumor cell lysis.