HLA-A*02:01-restricted NY-ESO-1 (157-165) peptide-MHC complex (NY-ESO-1:157-165/HLA-A*02:01)

The HLA-A*02:01-restricted NY-ESO-1 (157-165) peptide-MHC complex is a specific molecular target for cancer immunotherapy, consisting of a 9-amino acid peptide (SLLMWITQC) derived from the Cancer-Testis Antigen 1B (NY-ESO-1) presented by the HLA-A*02:01 allele (UniProt: P12101). NY-ESO-1 is a highly immunogenic protein typically expressed in the testis and placenta but aberrantly overexpressed in various cancers, including synovial sarcoma, melanoma, and multiple myeloma (PubMed: 24408344). Because normal adult somatic tissues lack NY-ESO-1 expression and the testis lacks MHC Class I expression, this complex serves as a highly tumor-specific target for CD8+ T-cells. Therapeutic interventions primarily utilize engineered T-cell receptor (TCR-T) therapies, such as afamitresgene autoleucel, which are designed to recognize this specific peptide-MHC complex with high affinity (FDA: Tecelra Approval, 2024). Upon recognition, the engineered T-cells undergo activation and expansion, leading to the targeted destruction of tumor cells through the release of perforins and granzymes (PubMed: 34161770). A significant challenge in targeting this epitope is ensuring TCR specificity to prevent lethal off-target cross-reactivity with similar peptides found in healthy tissues, such as the MAGE-A12 protein in the central nervous system (PubMed: 23644516).

Other names

NY-ESO-1 peptide 157-165SLLMWITQC-HLA-A*02:01 complexCTAG1B-derived epitopeNY-ESO-1 p157-165HLA-A2/NY-ESO-1 complex

Engineered T-cell receptor (TCR) therapy and peptide-based vaccines targeting the peptide-MHC complex to induce cytotoxic T-cell responses against tumor cells.