NY-ESO-1 peptide-HLA complex (NY-ESO-1/HLA)

NY-ESO-1 (Cancer/Testis Antigen 1B) is a highly immunogenic protein typically expressed in the germ cells of the testis and various malignant tumors, but it is notably absent in normal adult somatic tissues (UniProt: P12101). The therapeutic target is the specific complex formed when NY-ESO-1-derived peptides are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) Class I or Class II molecules (PubMed: 16144917). This peptide-MHC (pMHC) complex serves as a ligand for specific T-cell receptors (TCRs), making it a primary focus for TCR-engineered T-cell therapies and bispecific T-cell engagers. By targeting this site, the immune system can be directed to selectively identify and eliminate malignant cells expressing NY-ESO-1 while sparing healthy tissues. Clinical development has largely focused on the HLA-A*02:01-restricted presentation of the SLLMWITQC peptide, particularly in indications like synovial sarcoma and melanoma (NCT03132792). Recent therapeutic advancements, such as Afamitresgene autoleucel, utilize high-affinity TCRs to recognize this complex and trigger a potent anti-tumor immune response. The high specificity of the TCR for the NY-ESO-1/HLA complex is essential to minimize the risk of cross-reactivity with similar peptides presented on vital organs.

Other names

NY-ESO-1/MHC complexCTAG1B peptide-HLA complexNY-ESO-1 antigen-MHC complexNY-ESO-1–derived peptide binding site

T-cell receptor (TCR) mediated recognition of peptide-MHC complexes leading to T-cell activation, cytokine release, and targeted tumor cell lysis.