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Core 1 and extended core 1 O-glycans, most notably the Thomsen-Friedenreich (TF) antigen (Galβ1-3GalNAcα1-Ser/Thr), are truncated carbohydrate structures frequently overexpressed on the surface of tumor-associated glycoproteins like MUC1 (Ju et al., 2011). In healthy tissues, these glycans are typically elongated into complex branched structures, but dysregulated glycosylation in malignant cells leaves them exposed and accessible (Springer, 1984). These glycans play a critical role in cancer progression by facilitating cell-cell adhesion and interaction with vascular endothelium through binding with galectins, particularly Galectin-3, which promotes metastasis (Zhao et al., 2010). As tumor-associated carbohydrate antigens (TACAs), they serve as highly specific targets for immunotherapy, including monoclonal antibodies and CAR-T cell therapies (Goletz et al., 2015). Therapeutic strategies aim to induce antibody-dependent cellular cytotoxicity (ADCC) or disrupt the pro-metastatic signaling pathways mediated by these glycans. Clinical development has focused on targeting these epitopes to treat various solid tumors, including breast, lung, and ovarian cancers.
Induction of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and inhibition of galectin-mediated tumor cell adhesion and metastasis (Goletz et al., 2015; Zhao et al., 2010).
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