NY-ESO-1 peptide presented by Human Leukocyte Antigen A*02:01, A*02:05, and A*02:06 (NY-ESO-1/HLA-A*02)

NY-ESO-1 (Cancer/testis antigen 1B) is a highly immunogenic protein encoded by the CTAG1B gene, which is normally expressed only in the germ cells of the testis and placenta but is aberrantly expressed in various cancers, such as synovial sarcoma and melanoma (UniProt P78358, NIH). The therapeutic target is a specific peptide fragment of NY-ESO-1 (typically the SLLMWITQC sequence) presented on the cell surface by specific Human Leukocyte Antigen (HLA) Class I alleles, namely HLA-A*02:01, HLA-A*02:05, and HLA-A*02:06 (PubMed PMID: 34253558). This peptide-MHC (pMHC) complex is recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes, which then initiate the destruction of the tumor cell (PubMed PMID: 16144918). Because germ cells do not express HLA Class I molecules, they are not targeted by the immune system, making this pMHC complex a highly specific target for adoptive cell therapies like TCR-engineered T cells (TCR-T). Drugs like afamitresgene autoleucel have been developed to target this complex, providing a precision medicine approach for patients whose tumors express NY-ESO-1 and who possess the compatible HLA-A*02 genotypes (FDA, 2024). This target is particularly significant in the field of oncology as it represents one of the first successful applications of TCR-T therapy for solid tumors.

Other names

NY-ESO-1:157-165 peptide-HLA-A*02 complexCTAG1B-HLA-A*02 complexCancer/testis antigen 1B peptide-MHC complexSLLMWITQC-HLA-A*02 complexNY-ESO-1 peptide-MHC complex

T-cell receptor (TCR) mediated recognition and lysis of antigen-presenting tumor cells