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

New York esophageal squamous cell carcinoma 1 (NY-ESO-1), encoded by the CTAG1B gene, is a prominent cancer-testis antigen (CTA) whose expression is physiologically restricted to immune-privileged germ cells in the testis and placental trophoblasts (UniProt: P78358). Because these healthy tissues lack MHC Class I expression, the protein is effectively invisible to the immune system under normal conditions. However, NY-ESO-1 is aberrantly re-expressed in various solid tumors and hematological malignancies, where its immunodominant 9-amino acid peptide (SLLMWITQC) is processed and presented on the cell surface by HLA-A*02:01 and related HLA-A*02 alleles (PubMed: 9047241). This specific peptide-MHC complex has become a high-priority target for immunotherapy, particularly for T-cell receptor (TCR) engineered T-cell therapies. The clinical validity of this target was recently confirmed by the 2024 FDA approval of afamitresgene autoleucel (Tecelra) for the treatment of advanced synovial sarcoma (FDA.gov). By targeting an intracellularly derived peptide presented via MHC, these therapies can address oncogenic drivers that are not accessible to conventional monoclonal antibodies.

Other names

NY-ESO-1:157-165/HLA-A*02:01 complexCTAG1B peptide-MHC complexCancer/testis antigen 1B peptide-HLA-A*02:01NY-ESO-1-A2SLLMWITQC/HLA-A*02:01

Therapeutic agents such as TCR-engineered T-cells or bispecific T-cell engagers (ImmTACs) utilize high-affinity T-cell receptors (TCRs) to specifically bind the NY-ESO-1 peptide (SLLMWITQC) presented by HLA-A*02:01. This binding event triggers the formation of an immunological synapse, leading to T-cell activation, the release of cytotoxic granules (perforin and granzymes), and the subsequent lysis of the tumor cell (PubMed: 32534443).