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Branched Lewis B tumor-associated glycan (bLeB) is a novel carbohydrate antigen aberrantly expressed on the surface of various epithelial cancer cells, including gastric, colorectal, and pancreatic tumors (aacrjournals.org, 2025; glyconex.com.tw, 2025). Unlike the linear or unbranched Lewis antigens found in healthy tissues, the branched architecture of bLeB is highly tumor-specific, making it an attractive target for precision oncology (tiberend.com, 2025; bioworld.com, 2025). This glycan is frequently carried by key oncogenic proteins such as HER2 and PD-L1, where it may modulate signaling pathways involved in cell proliferation, survival, and immune evasion (aacrjournals.org, 2025; bioworld.com, 2025). Therapeutic development targeting bLeB includes the first-in-class antibody-drug conjugate (ADC) GNX1021, which delivers a cytotoxic payload directly to bLeB-positive cells (medpath.com, 2025; glyconex.com.tw, 2025). By targeting a glycan rather than a protein, these therapies can address patient populations that are ineligible for or resistant to traditional protein-targeted treatments, such as HER2-low gastric cancer (glyconex.com.tw, 2025; bioworld.com, 2025). Preclinical data suggest that bLeB-directed agents offer broad therapeutic coverage and a favorable safety profile due to the minimal expression of the branched glycan in normal tissues (tiberend.com, 2025; glyconex.com.tw, 2025).
Antibody-drug conjugate (ADC) delivery of cytotoxic payloads (e.g., monomethyl auristatin E) to cells expressing the glycan; monoclonal antibody-mediated tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
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