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

The NY-ESO-1 peptide-HLA class I complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy (PubMed: 25834524). NY-ESO-1, a cancer-testis antigen encoded by the CTAG1B gene, is typically expressed in germ cells but becomes aberrantly expressed in various malignancies, including melanoma, synovial sarcoma, and multiple myeloma (PubMed: 16144918). On the surface of dendritic cells or tumor cells, processed NY-ESO-1 peptides (such as the SLLMWITQC epitope) are presented within the groove of HLA class I molecules, most commonly HLA-A*02:01 (PubMed: 11015560). This complex is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T cells, initiating a targeted immune response against the tumor (PubMed: 21282551). Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies like afamitresgene autoleucel and letetresgene autoleucel, as well as vaccines designed to enhance dendritic cell presentation (ClinicalTrials.gov: NCT03132792). Because NY-ESO-1 expression is highly tumor-restricted, it is considered an ideal target for minimizing off-tumor toxicity, although cross-reactivity with similar self-peptides remains a primary safety consideration (PubMed: 23918359).

Other names

NY-ESO-1/HLA-A*02:01 complexNY-ESO-1/MHC class I complexCTAG1B/HLA complexNY-ESO-1 pMHC

Binding of engineered T-cell receptors (TCRs) or vaccine-induced endogenous TCRs to the specific NY-ESO-1 peptide presented by HLA class I molecules, triggering T-cell activation, cytokine release, and cytotoxic destruction of cells displaying the complex.