New York esophageal squamous cell carcinoma 1 peptide presented by Human Leukocyte Antigen A*02:01 or A*02:05 (NY-ESO-1/HLA-A*02)

NY-ESO-1 (New York esophageal squamous cell carcinoma 1), also known as Cancer/testis antigen 1B (CTAG1B), is a highly immunogenic protein whose expression is typically restricted to the germ cells of the testis and placenta (UniProt P12104). Because these tissues lack MHC Class I expression, the presentation of NY-ESO-1 peptides on HLA molecules is almost exclusively limited to cancer cells, making it a high-priority target for immunotherapy (PubMed: 16551870). The specific complex of the NY-ESO-1 157-165 peptide (SLLMWITQC) presented by HLA-A*02:01 or HLA-A*02:05 is the primary target for several engineered T-cell receptor (TCR) therapies, such as Afamitresgene autoleucel, which was FDA-approved in 2024 for synovial sarcoma (FDA.gov). These therapies involve modifying a patient's T cells to express a TCR that recognizes this peptide-MHC complex with high affinity, leading to targeted destruction of tumor cells. This target is particularly relevant in synovial sarcoma and myxoid/round cell liposarcoma, where NY-ESO-1 is frequently overexpressed. Beyond TCR-T cells, this complex is also targeted by therapeutic vaccines and bispecific T-cell engagers designed to redirect the immune system against NY-ESO-1-positive malignancies. Because the target is an intracellular protein presented as a peptide-MHC complex, it allows for the targeting of proteins that are not accessible to traditional antibody-based therapies.

Other names

NY-ESO-1/HLA-A*02:01 complexNY-ESO-1/HLA-A*02:05 complexCTAG1B peptide/HLA-A*02NY-ESO-1 157-165 peptide/HLA-A2Cancer/testis antigen 1B peptide/HLA-A*02

Engineered T-cell receptors (TCRs) or bispecific molecules bind specifically to the NY-ESO-1 peptide-HLA complex on the tumor cell surface, triggering T-cell activation, cytokine release, and cytotoxic lysis of the target cell.