Human leukocyte antigen A*02:01 presenting NY-ESO-1 peptide (HLA-A*02:01/NY-ESO-1)

The HLA-A*02:01-NY-ESO-1 complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy (PubMed: 11085993). It consists of the HLA-A*02:01 molecule (UniProt: P01892) presenting a 9-amino acid peptide, typically SLLMWITQC (NY-ESO-1 157-165), derived from the cancer-testis antigen NY-ESO-1 (UniProt: P78358). NY-ESO-1 is a highly immunogenic protein normally restricted to testicular germ cells, which do not express HLA molecules, making the complex a tumor-specific target when expressed in malignancies (PubMed: 16103331). This complex is frequently found on the surface of various solid tumors, including synovial sarcoma, melanoma, and certain lung cancers (PubMed: 28213373). Therapeutic interventions, such as TCR-engineered T-cell (TCR-T) therapies, are designed to recognize this specific pMHC with high affinity and specificity. Upon binding, these engineered T-cells initiate a cytotoxic response, releasing perforins and granzymes to induce apoptosis in the target cancer cells. The recent FDA approval of afamitresgene autoleucel (Tecelra) marks a significant milestone in targeting this complex for the treatment of advanced synovial sarcoma (FDA, 2024). Clinical monitoring for patients receiving these therapies involves verifying both the presence of the HLA-A*02:01 allele and the expression of the NY-ESO-1 protein in tumor tissue.

Other names

HLA-A2/NY-ESO-1NY-ESO-1/HLA-A*02:01 complexHLA-A*02:01-SLLMWITQCCTAG1B-HLA-A2 complexHLA-A*02:01 peptide-binding groove presenting NY-ESO-1

Engineered T-cell receptor (TCR) binding to the HLA-A*02:01/NY-ESO-1 peptide complex, triggering T-cell activation, expansion, and cytotoxic destruction of tumor cells expressing the antigen (FDA, 2024; PubMed: 28213373).