New York esophageal squamous cell carcinoma 1 (119–143) HLA-DR-restricted T-cell receptor (NY-ESO-1 (119–143) HLA-DR TCR) (NY-ESO-1 (119–143) HLA-DR TCR)

The New York esophageal squamous cell carcinoma 1 (119–143) HLA-DR-restricted T-cell receptor is a specialized immune receptor engineered for use in adoptive cell transfer therapies. It specifically recognizes a 25-amino acid peptide fragment (residues 119–143) of the NY-ESO-1 protein, a prominent cancer-testis antigen, when it is presented by HLA-DR class II molecules (Zarour et al., 2000, Cancer Research). NY-ESO-1 is an ideal target for immunotherapy because its expression is restricted to germ cells in the testis and placenta but is aberrantly upregulated in various cancers, including melanoma and synovial sarcoma (Hunder et al., 2008, NEJM). Unlike CD8+ TCRs that recognize MHC class I, this CD4+ TCR allows T cells to recognize tumor antigens in the context of MHC class II, which can lead to direct tumor lysis or the recruitment of other immune cells through cytokine secretion. In clinical applications, T cells are transduced with this TCR to create TCR-T therapies that can effectively target and eliminate NY-ESO-1-expressing tumor cells (Zhao et al., 2005, Journal of Immunotherapy). This approach is particularly valuable for enhancing the persistence and efficacy of the anti-tumor immune response by providing CD4+ T-cell help. Potential challenges include the requirement for specific HLA-DR alleles in patients and the risk of inflammatory side effects like cytokine release syndrome.

Other names

NY-ESO-1 119-143 specific TCRHLA-DRB1*01:01-restricted NY-ESO-1 TCRCTAG1B-specific CD4+ TCRNY-ESO-1-specific CD4+ T-cell receptor5B8 TCR

Engineered T-cells expressing the TCR recognize the NY-ESO-1 119-143 peptide presented by HLA-DR molecules on the surface of tumor cells, triggering T-cell activation, proliferation, and the release of cytotoxic granules and cytokines to eliminate the target cells (Zhao et al., 2005, Journal of Immunotherapy).