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

The New York esophageal squamous cell carcinoma 1 (NY-ESO-1) peptide–Human leukocyte antigen (HLA) class I complex is a pivotal target in cancer immunotherapy, specifically for T-cell receptor (TCR) engineered therapies (UniProt: P78358). NY-ESO-1 is a cancer-testis antigen (CTA) that is typically expressed in the immune-privileged germ cells of the testis but is aberrantly re-expressed in various cancers, such as synovial sarcoma, melanoma, and multiple myeloma (PubMed: 30012516). Because germ cells do not express HLA class I molecules, the presentation of NY-ESO-1-derived peptides (most commonly the SLLMWITQC epitope) on the cell surface is highly specific to tumor cells. Therapeutic agents like afamitresgene autoleucel (Tecelra) are designed to recognize this complex, triggering a potent cytotoxic T-cell response (FDA, 2024). The efficacy of these treatments is contingent upon the patient's HLA genotype, predominantly HLA-A*02:01, and the level of NY-ESO-1 expression in the tumor. While this target offers high specificity, challenges include potential immune escape through HLA downregulation and the management of treatment-induced cytokine release syndrome (PubMed: 26341548).

Other names

NY-ESO-1–HLA-A*02:01 complexCTAG1B–HLA-A2 complexCancer/testis antigen 1B peptide–MHC class I complexSLLMWITQC–HLA-A*02:01CTAG1B peptide–HLA complex

Targeted recognition of the peptide-MHC complex by engineered T-cell receptors (TCRs) or bispecific molecules, leading to T-cell activation and cytotoxic destruction of the tumor cell.