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

New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a prominent cancer-testis antigen (CTA) encoded by the CTAG1B gene [UniProt: P12101]. In healthy tissues, its expression is largely restricted to the testicular germ cells and placental trophoblasts, which lack HLA class I expression, thereby preventing T-cell recognition of normal tissues [PubMed: 9046814]. However, NY-ESO-1 is frequently overexpressed in a variety of cancers, including synovial sarcoma, melanoma, and multiple myeloma [PubMed: 34133884]. Intracellular NY-ESO-1 is processed into peptides, such as the immunodominant 157-165 epitope (SLLMWITQC), which are presented on the cell surface by HLA class I molecules, most commonly HLA-A*02:01 [PubMed: 9486510]. This peptide-HLA complex serves as a highly specific target for immunotherapies, including TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers [PubMed: 25583448]. These therapies, such as the FDA-approved afamitresgene autoleucel, aim to redirect the immune system to recognize and eliminate tumor cells expressing the NY-ESO-1 antigen while sparing healthy somatic tissues [FDA, 2024].

Other names

CTAG1BCancer/testis antigen 1BLAGE-2NY-ESO-1 peptide-MHC complexHLA-A*02:01/NY-ESO-1(157-165)

Recognition of the peptide-MHC complex by engineered T-cell receptors (TCRs) or bispecific molecules to induce T-cell mediated lysis of tumor cells.