NY-ESO-1-specific T-cell receptor (NY-ESO-1 TCR)

The NY-ESO-1-specific T-cell receptor is a synthetic or affinity-enhanced receptor engineered into patient T cells to target the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen. NY-ESO-1, encoded by the CTAG1B gene, is a cancer-testis antigen that is highly expressed in various tumors but restricted to immune-privileged germ cells in healthy tissues, making it an ideal target for immunotherapy (UniProt: P78358). The engineered TCR is designed to recognize a specific NY-ESO-1 peptide, most commonly the SLLMWITQC epitope, presented by the Human Leukocyte Antigen (HLA)-A*02:01 molecule on the surface of cancer cells (PubMed: 21282538). Upon binding, the TCR triggers a signaling cascade through the CD3 complex, leading to T-cell proliferation, cytokine production (such as IFN-gamma and TNF-alpha), and the direct lysis of tumor cells. This TCR-T cell approach is particularly effective against solid tumors like synovial sarcoma and myxoid/round cell liposarcoma, where NY-ESO-1 expression is prevalent (PubMed: 25623763). Clinical candidates utilizing this receptor, such as letetresgene autoleucel, have demonstrated the potential for durable clinical responses in patients with advanced malignancies (ClinicalTrials.gov: NCT03391778). However, therapeutic success depends on the presence of the specific HLA allele and the density of antigen expression on the tumor surface.

Other names

CTAG1B-specific T-cell receptor1G4 T-cell receptorNY-ESO-1-targeted TCRNew York esophageal squamous cell carcinoma 1-specific T-cell receptor

The engineered T-cell receptor recognizes the NY-ESO-1 peptide-HLA complex on tumor cells, initiating T-cell activation and cytotoxic destruction of the target cell.