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Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), also known as KOC1 (KH domain-containing protein overexpressed in cancer), is an oncofetal protein that plays a significant role in RNA trafficking and translational control during embryogenesis (UniProt: P67870). While its expression is minimal or absent in normal adult tissues, it is highly upregulated in various aggressive malignancies, including esophageal, pancreatic, and lung cancers, where it often correlates with poor prognosis and metastasis (Taniuchi et al., 2012, Clin Cancer Res). The presentation of specific IGF2BP3-derived epitopes, such as the KOC1-204 peptide (KIFVGGLSV), by the HLA-A*2402 molecule creates a unique target for T-cell-mediated immunotherapy (Suda et al., 2007, Cancer Sci). Therapeutic strategies, primarily peptide vaccines, are designed to elicit a robust cytotoxic T lymphocyte (CTL) response against tumor cells harboring this complex. Because the HLA-A*2402 allele is highly prevalent in East Asian populations, this target represents a significant opportunity for personalized cancer treatment in those regions. Clinical trials have demonstrated that targeting this epitope can induce specific immune responses with a manageable safety profile in patients with advanced solid tumors (Kono et al., 2009, Cancer Sci).
Induction of peptide-specific cytotoxic T lymphocytes (CTLs) that recognize and lyse tumor cells presenting the IGF2BP3 epitope via HLA-A*2402.
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