Cancer-testis antigen 1 (NY-ESO-1) peptide–HLA-A*02:01 complex (NY-ESO-1/HLA-A*02:01 complex)

The Cancer-testis antigen 1 (NY-ESO-1) peptide–HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy. It consists of a 9-amino acid epitope (SLLMWITQC, residues 157-165) derived from the NY-ESO-1 protein, which is presented on the cell surface by the HLA-A*02:01 allele [1.1.1, 1.1.4]. NY-ESO-1 is a cancer-testis antigen (CTA) encoded by the CTAG1A and CTAG1B genes, characterized by its restricted expression in germ cells of the testis and placenta and its aberrant re-expression in various cancers [1.2.1, 1.4.1]. Because normal germ cells do not express MHC class I molecules, the NY-ESO-1/HLA complex is highly tumor-specific, minimizing the risk of on-target off-tumor toxicity in healthy tissues [1.2.1, 1.3.2]. This complex is recognized by specific T-cell receptors (TCRs), making it a primary target for TCR-engineered T-cell (TCR-T) therapies and bispecific TCR-mimetic molecules [1.2.1, 1.2.3]. Clinical applications have focused on treating NY-ESO-1-positive malignancies such as synovial sarcoma, melanoma, and multiple myeloma [1.2.2, 1.3.2]. Drugs targeting this complex, such as letetresgene autoleucel, aim to induce potent cytotoxic T-lymphocyte responses to eliminate tumor cells [1.3.2, 1.3.3].

Other names

NY-ESO-1/HLA-A2 complexCTAG1A/HLA-A*02:01 complexSLLMWITQC-HLA-A*02:01 complexNY-ESO-1 157-165 peptide-MHC complexCTAG1B/HLA-A*02:01 complex

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