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

New York esophageal squamous cell carcinoma 1 (NY-ESO-1), encoded by the CTAG1B gene (UniProt P78358), is a prominent member of the cancer-testis antigen family. Under physiological conditions, its expression is restricted to the germ cells of the testis and the trophoblasts of the placenta, which are immune-privileged sites that lack HLA class I expression, effectively preventing T-cell recognition in healthy tissues (PubMed: 25533380). However, NY-ESO-1 is aberrantly upregulated in various malignancies, including synovial sarcoma, melanoma, and multiple myeloma, where its derived peptides are processed and presented on the cell surface by HLA class I molecules, most commonly HLA-A*02:01 (PubMed: 16144918). This specific peptide-HLA complex serves as a highly specific target for cancer immunotherapy, particularly for T-cell receptor (TCR) engineered T-cell therapies. Therapeutic agents such as Afamitresgene autoleucel are designed to recognize this complex with high affinity, triggering the activation of cytotoxic T-lymphocytes and the subsequent lysis of antigen-expressing tumor cells (ClinicalTrials.gov: NCT04044755). Due to its high tumor specificity and strong immunogenicity, the NY-ESO-1/HLA complex is a primary candidate for precision oncology and the development of therapeutic cancer vaccines.

Other names

CTAG1B peptide-HLA complexNY-ESO-1/MHC class I complexCancer/testis antigen 1B peptide-HLA complexNY-ESO-1/HLA-A*02:01LAGE-2 peptide-HLA complex

Recognition of the peptide-HLA complex by engineered or endogenous T-cell receptors (TCRs), leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of antigen-expressing tumor cells.