HLA-A*24:02-restricted NY-ESO-1 (158-166) peptide-MHC complex (HLA-A*24/NY-ESO-1(158-166))

The HLA-A*24:02-restricted NY-ESO-1 (158-166) peptide-MHC complex is a specific molecular target used in cancer immunotherapy, particularly in populations where the HLA-A*24 allele is prevalent, such as in East Asia (PMID: 11877306). It consists of the HLA-A*24:02 molecule presenting a 9-amino acid epitope (LLMWITQCF) derived from the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) protein (PMID: 15150593). NY-ESO-1 is a well-characterized cancer-testis antigen that is highly expressed in various malignancies but restricted to germ cells in healthy adults, making it an ideal target for minimizing off-tumor effects (PMID: 25108347). Therapeutic strategies targeting this complex primarily involve T-cell receptor (TCR) engineered T-cell therapies, such as TBI-1301, which are designed to recognize and kill tumor cells presenting this specific antigen (ClinicalTrials.gov NCT02869217). Clinical development focuses on solid tumors like synovial sarcoma and melanoma, where NY-ESO-1 expression is frequent (PMID: 33033110). This target represents a precision medicine approach, requiring patient screening for both the specific HLA genotype and tumor antigen expression. The interaction between the engineered TCR and the pMHC complex triggers a robust immune response, leading to the release of perforins and granzymes that induce apoptosis in the target cancer cells. Despite its promise, challenges include potential off-target cross-reactivity and the immunosuppressive tumor microenvironment that can limit T-cell persistence and activity.

Other names

HLA-A*24:02/NY-ESO-1 (158-166)NY-ESO-1 p158-166/HLA-A*24:02A*2402-NY-ESO-1-158LLMWITQCF/HLA-A*24:02 complexMHC class I HLA-A*24 presenting NY-ESO-1 158-166 epitope

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, triggering cytotoxic T-cell activation and targeted lysis of tumor cells.