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

The NY-ESO-1–HLA class I complex is a highly specific tumor-associated antigen formed by the presentation of peptides derived from the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) protein on the surface of cancer cells via Human Leukocyte Antigen (HLA) molecules, most commonly HLA-A*02:01 (Chen et al., 1997, PNAS; Jäger et al., 1998, J Exp Med). NY-ESO-1 is a member of the cancer-testis antigen (CTA) family, which is characterized by restricted expression in normal adult tissues (primarily the testis and placenta) but frequent re-expression in various malignancies, including synovial sarcoma and melanoma (Thomas et al., 2018, Front Immunol). Because germ cells in the testis do not express HLA class I molecules, the NY-ESO-1–HLA complex is effectively tumor-specific, making it an ideal target for immunotherapy with minimal risk of off-tumor toxicity (Gnjatic et al., 2006, Adv Cancer Res). Therapeutic interventions targeting this complex include T-cell receptor (TCR)-engineered T cells, such as the FDA-approved afamitresgene autoleucel, and bispecific T-cell engagers designed to redirect T-cell cytotoxicity specifically toward cells presenting the NY-ESO-1 peptide (D'Angelo et al., 2018, Cancer Discovery; FDA, 2024). These therapies rely on the precise recognition of the peptide-MHC interface, requiring patients to be screened for both NY-ESO-1 expression and the appropriate HLA allele (Pollack et al., 2020, J Clin Oncol).

Other names

NY-ESO-1 peptide-MHC complexCTAG1B peptide-HLA complexNY-ESO-1/HLA-A*02:01 complexSLLMWITQC-HLA-A*02:01 complex

T-cell receptor (TCR) engineered T-cell therapy (TCR-T), Bispecific T-cell engager (ImmTAC), TCR-mimetic antibody-mediated cytotoxicity