NY-ESO-1-derived peptides presented by HLA-DR4 (NY-ESO-1/HLA-DR4)

NY-ESO-1-derived peptides presented by HLA-DR4 (specifically HLA-DRB1*04) constitute a specific peptide-MHC (pMHC) class II complex that serves as a target for cancer immunotherapy. NY-ESO-1, also known as Cancer-testis antigen 1B (CTAG1B), is an immunodominant protein typically restricted to the testis but aberrantly expressed in various malignancies such as melanoma, synovial sarcoma, and ovarian cancer (Gnjatic et al., 2006, PMID: 16877111). The presentation of specific epitopes, most notably the NY-ESO-1(116-135) peptide, by HLA-DR4 molecules is essential for the activation of CD4+ T helper cells (Zarour et al., 2000, PMID: 10919471). These CD4+ T cells play a pivotal role in the anti-tumor response by providing help to CD8+ cytotoxic T cells and potentially exerting direct cytotoxic effects on MHC class II-positive tumor cells (Zarour et al., 2002, PMID: 11807631). Therapeutic interventions targeting this complex include T-cell receptor (TCR) engineered T-cell therapies and various vaccine platforms, such as CMB305, which aim to expand the population of NY-ESO-1-specific T cells in patients (Pollack et al., 2020, PMID: 32814518). Because NY-ESO-1 is not expressed in essential somatic tissues, targeting this complex minimizes the risk of on-target, off-tumor toxicity, making it a highly attractive candidate for precision oncology.

Other names

NY-ESO-1/HLA-DRB1*04 complexCTAG1B/HLA-DR4NY-ESO-1(116-135)/HLA-DR4NY-ESO-1 peptide-MHC class II complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to the activation of CD4+ T helper cells and subsequent anti-tumor immune responses.