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New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a well-characterized cancer-testis antigen (CTA) encoded by the CTAG1B gene (UniProt P78358). In healthy individuals, its expression is restricted to germ cells in the testis and placenta, which are considered immune-privileged sites due to the lack of MHC Class I expression (Chen et al., 1997, PMID: 9034906). In contrast, NY-ESO-1 is aberrantly expressed in a wide range of tumors, including synovial sarcoma, melanoma, and multiple myeloma, making it a highly specific target for immunotherapy (Gnjatic et al., 2006, PMID: 16551862). The therapeutic target consists of a specific immunodominant peptide (typically the 157-165 sequence, SLLMWITQC) presented by the Human Leukocyte Antigen A*02 (HLA-A*02) on the surface of cancer cells (Jäger et al., 1998, PMID: 9491737). This peptide-MHC complex is recognized by high-affinity T-cell receptors (TCRs), which are utilized in the development of TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers (D'Angelo et al., 2018, PMID: 29531200). These therapeutic approaches, such as the FDA-approved afamitresgene autoleucel, aim to harness the patient's immune system to selectively identify and eliminate NY-ESO-1-positive tumor cells while minimizing damage to healthy tissues (FDA, 2024).
Recognition of the specific peptide-MHC complex by engineered T-cell receptors (TCRs) or bispecific TCR-adapter molecules, leading to T-cell activation, cytokine release, and targeted lysis of NY-ESO-1-expressing tumor cells.
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