NY-ESO-1-specific CD4+ T-cell receptor

NY-ESO-1-specific CD4+ T-cell receptors are engineered or naturally occurring immune receptors that specifically recognize the cancer-testis antigen NY-ESO-1 (CTAG1B) when presented by HLA Class II molecules (UniProt: P78358). Unlike CD8+ TCRs that recognize peptides on HLA Class I, these receptors target peptides such as NY-ESO-1 157-170 presented by HLA-DPB1*04:01, a common Class II allele (PubMed: 15155838). The biological function of these receptors is to mediate the activation of CD4+ T cells, which then orchestrate an immune response through the secretion of cytokines like interferon-gamma and tumor necrosis factor-alpha (PubMed: 27532018). In some cases, these CD4+ T cells can also exhibit direct cytotoxic activity against tumor cells. In therapeutic applications, these TCRs are used to engineer T cells (TCR-T therapy) to treat NY-ESO-1-positive malignancies, including synovial sarcoma, melanoma, and multiple myeloma (PubMed: 30635440). The primary mechanism involves the high-affinity binding of the TCR to the peptide-MHC complex, triggering downstream signaling that leads to tumor cell recognition and destruction. Clinical development of these receptors aims to provide a more comprehensive immune response by engaging the helper T-cell compartment alongside or instead of the traditional CD8+ cytotoxic response.

Other names

NY-ESO-1-specific HLA-class II-restricted T-cell receptorCTAG1B-specific CD4+ TCRHLA-DP4-restricted NY-ESO-1 TCRNY-ESO-1 peptide-HLA class II complex-specific TCR

Recognition of NY-ESO-1 peptide-HLA class II complexes leading to T-cell activation and anti-tumor effector functions.