NY-ESO-1 peptide-MHC complex (NY-ESO-1/MHC)

The NY-ESO-1 peptide-MHC complex is a critical therapeutic target in oncology, particularly for T-cell receptor (TCR) based interventions. NY-ESO-1, encoded by the CTAG1B gene, is a cancer-testis antigen that is highly expressed in several aggressive malignancies, including synovial sarcoma, melanoma, and certain types of lung cancer, while remaining largely absent in healthy adult tissues (UniProt P78358). The target specifically refers to the processed NY-ESO-1 peptide (most commonly the 157-165 SLLMWITQC epitope) presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, typically HLA-A*02:01 (PubMed: 11015561). Therapeutic strategies such as TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers are designed to bind this complex with high affinity and specificity, bypassing the limitations of traditional antibody-based approaches that only target surface proteins. By recognizing intracellularly derived peptides presented on MHC, these therapies can effectively direct the immune system to destroy tumor cells. The clinical validation of this target was recently solidified by the FDA approval of afamitresgene autoleucel for the treatment of advanced synovial sarcoma (FDA, 2024). Safety considerations for therapies targeting this complex include cytokine release syndrome and potential off-target cross-reactivity with similar endogenous peptides (PubMed: 30012526).

Other names

NY-ESO-1 peptide-HLA-A*02:01 complexCTAG1B-HLA complexCancer/testis antigen 1B peptide-MHC complexSLLMWITQC-HLA-A*02:01T-cell receptors specific for NY-ESO-1 peptide–MHC complexes

T-cell receptor-mediated recognition of the NY-ESO-1 peptide-MHC complex leading to T-cell activation and tumor cell lysis.