New York esophageal squamous cell carcinoma 1 peptide–Major Histocompatibility Complex class I complex (NY-ESO-1-pMHC)

The New York esophageal squamous cell carcinoma 1 (NY-ESO-1) peptide–Major Histocompatibility Complex (MHC) class I complex is a critical target in cancer immunotherapy, particularly for TCR-engineered T-cell (TCR-T) therapies. NY-ESO-1 is a cancer-testis antigen encoded by the CTAG1B gene, which is normally expressed only in the germ cells of the testis and placenta—tissues that lack MHC class I expression and are thus protected from T-cell attack [PMID: 9034103, PMID: 24408344]. In various malignancies, such as synovial sarcoma and melanoma, NY-ESO-1 is aberrantly expressed, and its intracellular proteins are processed into peptides that are presented on the cell surface by MHC class I molecules, most frequently HLA-A*02:01 [PMID: 16144957]. This specific peptide-MHC (pMHC) complex, often featuring the immunodominant SLLMWITQC epitope, serves as a unique signature for tumor cells. Drugs like afamitresgene autoleucel are designed to recognize this complex via high-affinity T-cell receptors, leading to the activation of cytotoxic T-cells and subsequent tumor lysis [PMID: 38537575]. Because of its restricted expression in healthy tissues and high prevalence in certain aggressive cancers, this complex is considered an ideal target for minimizing off-target toxicity while maximizing therapeutic efficacy.

Other names

NY-ESO-1/HLA-A*02:01 complexCTAG1B peptide-MHC complexNY-ESO-1-derived peptide-HLA complexNY-ESO-1 pMHC

Targeted recognition by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce cytotoxic T-lymphocyte mediated destruction of tumor cells.