New York esophageal squamous cell carcinoma 1 peptide–Major Histocompatibility Complex (NY-ESO-1 peptide–MHC) (NY-ESO-1–MHC)

NY-ESO-1 (New York esophageal squamous cell carcinoma 1), encoded by the CTAG1B gene, is a prominent member of the cancer-testis antigen (CTA) family (UniProt P12101). Under physiological conditions, its expression is restricted to testicular germ cells and placental trophoblasts, which lack MHC Class I expression, thereby preventing T-cell recognition of healthy tissues (PubMed: 16551957). However, NY-ESO-1 is frequently overexpressed in various malignancies, such as synovial sarcoma, melanoma, and non-small cell lung cancer, where its intracellular proteins are processed into peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 (PubMed: 24942756). This peptide-MHC complex serves as a highly specific therapeutic target for engineered T-cell receptor (TCR) therapies, such as afamitresgene autoleucel, which was FDA-approved in 2024 for synovial sarcoma (FDA.gov). These therapies utilize modified TCRs to bind the specific NY-ESO-1 peptide-MHC complex, triggering T-cell activation, cytokine release, and the direct lysis of tumor cells (PubMed: 30013095).

Other names

CTAG1B peptide-MHCNY-ESO-1/HLA-A*02:01 complexCancer/testis antigen 1B peptide-MHCLAGE-2 peptide-MHCNY-ESO-1 SLLMWITQC-HLA-A2 complex

Recognition of the specific NY-ESO-1 peptide presented by MHC Class I molecules by engineered T-cell receptors (TCRs) or TCR-like antibodies, leading to targeted cytotoxicity (PubMed: 30013095).