New York esophageal squamous cell carcinoma 1 peptide-MHC class I complex (NY-ESO-1/MHC)

The New York esophageal squamous cell carcinoma 1 (NY-ESO-1) peptide presented by MHC class I is a major target for cancer immunotherapy, particularly in the development of T-cell receptor (TCR) engineered T-cell therapies. NY-ESO-1 is a member of the cancer-testis antigen family, encoded by the CTAG1B gene, and is characterized by its restricted expression in the testis and placenta—tissues that do not express MHC class I—and its aberrant expression in various cancers (UniProt P78358). This expression pattern makes the NY-ESO-1 peptide-MHC complex a highly specific tumor antigen with a low risk of off-target toxicity in normal tissues. In clinical settings, the most common epitope targeted is the SLLMWITQC peptide presented by the HLA-A*02:01 allele (PubMed: 21282551). Drugs like afamitresgene autoleucel (Tecelra) are designed to recognize this complex, enabling T cells to identify and destroy tumor cells that present the antigen on their surface (FDA, 2024). While highly effective in specific solid tumors like synovial sarcoma, the therapy's applicability is limited by the requirement for patients to possess the correct HLA genotype and the potential for tumor escape via MHC downregulation.

Other names

NY-ESO-1/HLA complexCTAG1B peptide-MHCCancer/testis antigen 1B peptide-HLA complexSLLMWITQC-HLA-A*02:01 complex

The mechanism of action involves the specific recognition of the NY-ESO-1 peptide (typically the SLLMWITQC epitope) presented within the HLA-A*02:01 molecule by an engineered T-cell receptor (TCR) or a bispecific T-cell engager. This recognition forms an immunological synapse, leading to the activation of the T cell and the subsequent release of cytotoxic granules, such as perforin and granzymes, which induce programmed cell death in the target tumor cell (PubMed: 21282551).