NY-ESO-1 peptide-HLA-A*02 complex (NY-ESO-1/HLA-A2)

NY-ESO-1 (New York esophageal squamous cell carcinoma 1), encoded by the CTAG1B gene, is a prominent cancer-testis antigen (CTA) that is highly expressed in various malignancies but restricted to germ cells in healthy adults (UniProt: P12101). The specific immunodominant peptide SLLMWITQC (residues 157-165) is presented on the surface of tumor cells by the Human Leukocyte Antigen (HLA) alleles A*02:01 or A*02:06 (PubMed: 16144918). This peptide-MHC complex serves as a highly specific therapeutic target because normal germ cells in the testis lack HLA Class I expression, thereby minimizing the risk of on-target, off-tumor toxicity. Therapeutic interventions primarily utilize engineered T-cell receptor (TCR) therapies, such as the FDA-approved afamitresgene autoleucel, which are designed to recognize this complex and trigger a potent T-cell mediated anti-tumor response (FDA, 2024). Clinical development has focused on solid tumors like synovial sarcoma, where NY-ESO-1 expression is prevalent. Patient eligibility for these therapies requires confirmation of both the specific HLA-A*02 genotype and high tumor expression of the NY-ESO-1 protein (ClinicalTrials.gov: NCT04044859).

Other names

Cancer/testis antigen 1B (CTAG1B)NY-ESO-1 (157-165) peptideSLLMWITQC-HLA-A*02:01 complexSLLMWITQC-HLA-A*02:06 complexNew York esophageal squamous cell carcinoma 1CTAG1

T-cell receptor (TCR) mediated recognition and activation leading to tumor cell lysis