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The HLA-A*24:02-presented URLC10-derived peptide is a peptide-major histocompatibility complex (pMHC) that serves as a specific target for cancer immunotherapy, particularly in East Asian populations where the HLA-A*24:02 allele is highly prevalent (PMID: 19138344). URLC10 (Up-regulated in lung cancer 10), also known as C19orf54, is a cancer-testis antigen that is significantly overexpressed in various malignancies, including non-small cell lung cancer, pancreatic cancer, and esophageal cancer, while remaining largely absent in normal adult tissues except for the testis (PMID: 21406405). The specific epitope, typically the 9-mer URLC10-177 (SYWGVIGAV), is processed and presented on the cell surface by HLA-A*24:02, allowing for recognition by the T-cell receptors (TCRs) of cytotoxic T lymphocytes (CTLs). Therapeutic strategies targeting this complex include peptide-based vaccines designed to elicit an endogenous CTL response and adoptive cell therapies, such as TCR-engineered T cells (TCR-T), which provide a direct means of eliminating tumor cells (PMID: 25100374). Clinical trials have demonstrated that targeting this pMHC can induce tumor-specific immune responses and may correlate with improved clinical outcomes in patients with advanced disease (PMID: 22430473). Because URLC10 expression is highly restricted to tumor cells, it is considered a promising target with a potentially low risk of on-target, off-tumor toxicity, although challenges such as HLA downregulation and the immunosuppressive tumor microenvironment persist.
Induction of cytotoxic T lymphocyte-mediated lysis of tumor cells expressing the URLC10/HLA-A*24:02 complex.
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