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

The NY-ESO-1-specific T-cell receptor (TCR) is a specialized heterodimeric protein complex engineered to recognize the cancer-testis antigen NY-ESO-1 (New York esophageal squamous cell carcinoma 1). NY-ESO-1 is highly expressed in various aggressive malignancies, such as synovial sarcoma and melanoma, but is restricted to germ cells in healthy adults, making it an ideal target for immunotherapy [National Cancer Institute, 2023]. The TCR functions by binding to a specific NY-ESO-1 peptide fragment (typically SLLMWITQC) presented on the cell surface by the Human Leukocyte Antigen (HLA)-A*02:01 molecule [Nature Reviews Cancer, 2021]. This binding event initiates a signaling cascade through the CD3 complex that activates the T-cell, leading to the secretion of pro-inflammatory cytokines and the direct lysis of tumor cells via perforin and granzymes [Journal of Clinical Oncology, 2022]. Therapeutic applications primarily involve TCR-engineered T-cell (TCR-T) therapies, such as the FDA-approved afamitresgene autoleucel, which reprogram a patient's own immune cells to express this specific receptor [FDA, 2024]. Clinical trials have demonstrated that targeting NY-ESO-1 with these receptors can induce significant and durable responses in patients with advanced solid tumors [The Lancet, 2023].

Other names

NY-ESO-1 TCR1G4 TCRNY-ESO-1/LAGE-1a-specific T-cell receptorCTAG1B-specific T-cell receptor

Engineered T-cell receptor binding to NY-ESO-1 peptide-HLA complex leading to T-cell mediated tumor cell lysis.