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

NY-ESO-1 (New York esophageal squamous cell carcinoma 1) is a prominent cancer-testis antigen encoded by the CTAG1B gene (UniProt P78358). In healthy tissues, its expression is restricted to the testis and placenta, which are immune-privileged sites due to the lack of MHC Class I expression. However, NY-ESO-1 is aberrantly expressed in various malignancies, including synovial sarcoma, melanoma, and multiple myeloma (PMID: 30104244). The NY-ESO-1 peptide-MHC complex forms when intracellular NY-ESO-1 proteins are degraded by the proteasome and the resulting peptides, such as the SLLMWITQC decamer, are presented on the cell surface by HLA molecules, typically HLA-A*02:01. This complex serves as a highly specific target for T-cell receptor (TCR)-based immunotherapies, which can recognize intracellular antigens that are inaccessible to traditional antibody-based or CAR-T therapies. Drugs like afamitresgene autoleucel (Tecelra) utilize engineered TCRs to bind this complex, triggering T-cell mediated lysis of the tumor cells (FDA, 2024). Clinical efficacy is dependent on both the expression of the NY-ESO-1 antigen and the presence of the specific HLA allele in the patient. Safety considerations primarily involve cytokine release syndrome and potential off-target effects if the TCR cross-reacts with similar peptides in normal tissues (PMID: 32692590).

Other names

CTAG1B peptide-MHCNY-ESO-1/HLA-A2 complexCancer/testis antigen 1B peptide-MHCNY-ESO-1 pMHC

T-cell receptor (TCR) mediated recognition of peptide-MHC complexes leading to T-cell activation and tumor cell lysis