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

The New York esophageal squamous cell carcinoma 1 (NY-ESO-1) SLLMWITQC peptide presented by Human Leukocyte Antigen A*02:01 (HLA-A*02:01) is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy. NY-ESO-1, encoded by the CTAG1B gene, is a cancer-testis antigen that is highly expressed in various solid tumors but absent in normal adult tissues except for the immune-privileged testis and placenta (UniProt P12101). The SLLMWITQC epitope, corresponding to residues 157-165, is a dominant immunogenic peptide that is processed and presented on the cell surface by the HLA-A*02:01 allele (PubMed 11160756). This complex is recognized by specific T-cell receptors (TCRs), making it a primary target for TCR-engineered T-cell (TCR-T) therapies and bispecific molecules. Drugs like afamitresgene autoleucel have been developed to target this complex, showing significant efficacy in treating synovial sarcoma and other NY-ESO-1-expressing malignancies (FDA 2024). The therapeutic approach relies on the high specificity of the TCR for the pMHC, which triggers T-cell activation and subsequent tumor cell lysis. However, challenges such as off-target cross-reactivity with similar endogenous peptides and the requirement for patients to be HLA-A*02:01 positive remain significant considerations for clinical application (PubMed 34253558). Overall, this target represents a paradigm for precision immunotherapy in solid tumors.

Other names

NY-ESO-1 (157-165) peptideCTAG1B (157-165) peptideNY-ESO-1:157-165/HLA-A2 complexSLLMWITQC-HLA-A*02:01Cancer/testis antigen 1B peptide

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and cytotoxic lysis of tumor cells.