NY-ESO-1 peptide (157-165) presented by HLA-A*02:01 complex (NY-ESO-1/HLA-A*02:01)

The NY-ESO-1 peptide presented by HLA-A*02:01 complex is a highly specific therapeutic target in oncology, consisting of a 9-amino acid epitope (SLLMWITQC) derived from the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) protein. NY-ESO-1 is a cancer-testis antigen (CTA) that is typically restricted to immune-privileged germ cells but is frequently overexpressed in various solid tumors, such as synovial sarcoma and melanoma. This intracellular protein is processed into peptides and presented on the cell surface by the Major Histocompatibility Complex (MHC) class I molecule HLA-A*02:01, allowing it to be recognized by the immune system. Therapeutic interventions, primarily T-cell receptor (TCR) engineered T-cell therapies like letetresgene autoleucel, are designed to bind this specific peptide-MHC complex to induce potent anti-tumor responses. Because of its restricted expression in normal tissues, targeting this complex offers a high therapeutic index, although clinical challenges include the requirement for HLA-A*02:01 patient matching and the management of treatment-related toxicities like cytokine release syndrome.

Other names

NY-ESO-1 157-165/HLA-A*02:01SLLMWITQC/HLA-A*02:01CTAG1B/HLA-A*02:01NY-ESO-1/HLA-A2 complexNY-ESO-1 peptide-MHC complex

The mechanism of action involves the recognition of the specific NY-ESO-1 peptide (SLLMWITQC) presented by the HLA-A*02:01 molecule on the surface of tumor cells by engineered T-cell receptors (TCRs). This recognition triggers T-cell activation, leading to the release of cytotoxic molecules such as perforin and granzymes, as well as pro-inflammatory cytokines like interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), which ultimately results in the lysis of the target cancer cells.