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

New York esophageal squamous cell carcinoma 1 (NY-ESO-1), encoded by the CTAG1B gene, is a prominent cancer-testis antigen (CTA) that is highly immunogenic [1]. In healthy tissues, its expression is restricted to the germ cells of the testis and placenta, which are immune-privileged sites that do not express MHC Class I molecules, thereby preventing autoimmune recognition [2]. However, NY-ESO-1 is aberrantly re-expressed in a variety of malignancies, including synovial sarcoma and melanoma, where it serves as a specific tumor-associated antigen [3]. The specific epitope SLLMWITQC (amino acids 157-165) is processed and presented on the tumor cell surface by the Human Leukocyte Antigen A*02:01 (HLA-A*02:01) allele [4]. This peptide-MHC complex is a major target for adoptive cell therapies, particularly T-cell receptor (TCR) engineered T-cells like afamitresgene autoleucel, which was the first TCR-T therapy to receive FDA approval [5][6]. By targeting this specific complex, therapies can induce a potent and selective anti-tumor immune response while minimizing damage to healthy somatic tissues [7].

Other names

CTAG1BCancer/testis antigen 1BNY-ESO-1:157-165 peptideSLLMWITQC-HLA-A*02:01 complexNY-ESO-1/HLA-A2 complex

Engineered T-cell receptors (TCRs) or bispecific molecules specifically recognize and bind the NY-ESO-1 SLLMWITQC peptide presented by HLA-A*02:01, leading to T-cell activation, secretion of pro-inflammatory cytokines, and direct cytotoxic lysis of the tumor cell.