New York esophageal squamous cell carcinoma 1 peptide–Human leukocyte antigen class I complex (NY-ESO-1–HLA-I)

NY-ESO-1 (New York esophageal squamous cell carcinoma 1), encoded by the CTAG1B gene, is a prominent member of the cancer-testis antigen (CTA) family (UniProt P78358). Its expression is typically restricted to the immune-privileged germ cells of the testis and placental trophoblasts, which lack HLA class I expression, thereby preventing autoimmune targeting (PubMed: 16341015). However, NY-ESO-1 is frequently overexpressed in various cancers, including synovial sarcoma, melanoma, and multiple myeloma, where it is processed into peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, most notably HLA-A*02:01 (PubMed: 25103341). The NY-ESO-1 peptide–HLA class I complex serves as a highly specific target for immunotherapy, particularly T-cell receptor (TCR) engineered T-cell therapies and bispecific T-cell engagers (ImmTACs). The recent FDA approval of afamitresgene autoleucel (Tecelra) for synovial sarcoma highlights the clinical significance of this target in treating solid tumors (FDA.gov, 2024). Therapeutic strategies focus on the high-affinity recognition of the SLLMWITQC peptide-MHC complex to trigger potent T-cell mediated cytotoxicity against malignant cells.

Other names

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

Engineered T-cell receptors (TCRs) or bispecific molecules bind specifically to the NY-ESO-1 peptide presented by HLA class I molecules, triggering T-cell activation, secretion of inflammatory cytokines, and granzyme/perforin-mediated lysis of the target tumor cell.