New York esophageal squamous cell carcinoma 1 (NY-ESO-1) (157–165) peptide presented by Human Leukocyte Antigen A*02:01 (HLA-A*02:01) (NY-ESO-1 (157–165)/HLA-A*02:01)

The New York esophageal squamous cell carcinoma 1 (NY-ESO-1) (157–165) peptide presented by Human Leukocyte Antigen A*02:01 (HLA-A*02:01) is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy. NY-ESO-1, encoded by the CTAG1B gene, is a cancer-testis antigen (CTA) that is normally expressed only in the testis and placenta but is aberrantly expressed in a wide range of malignancies, including synovial sarcoma, melanoma, and multiple myeloma (UniProt P12101). The specific 9-amino acid peptide sequence SLLMWITQC (residues 157–165) is processed and presented on the cell surface by the HLA-A*02:01 allele, which is prevalent in approximately 40-50% of the Caucasian population (PubMed: 10746838). This complex is recognized with high affinity by engineered T-cell receptors (TCRs) in TCR-T cell therapies and by bispecific T-cell engagers, such as ImmTACs. Because NY-ESO-1 is not expressed in essential normal tissues, targeting this pMHC complex provides a high degree of tumor specificity and a favorable safety profile. Clinical applications include the FDA-approved afamitresgene autoleucel for synovial sarcoma, which utilizes a TCR engineered to recognize this specific complex (FDA: Tecelra). Therapeutic challenges include potential off-target cross-reactivity with similar endogenous peptides and the management of cytokine release syndrome (CRS) following T-cell activation.

Other names

NY-ESO-1 (157-165)/HLA-A2 complexSLLMWITQC-HLA-A*02:01CTAG1B peptide-MHC complexHLA-A2/NY-ESO-1(157-165)NY-ESO-1:157-165/HLA-A*02:01

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and targeted tumor cell lysis.