Branched Lewis Y tumor-associated glycan (bLeY)

Branched Lewis Y (bLeY) is a tumor-associated carbohydrate antigen (TACA) belonging to the Lewis blood group system, characterized by a complex difucosylated oligosaccharide structure [1.3.2, 1.4.1]. It is frequently overexpressed on the surface of various epithelial malignancies, including gastric, colorectal, pancreatic, and breast cancers, where it plays a critical role in mediating cell-cell adhesion and modulating oncogenic signaling pathways [1.1.2, 1.3.1]. In healthy individuals, bLeY expression is largely restricted to specific epithelial cells of the gastrointestinal tract and certain hematopoietic cells, making it a viable but challenging target for precision oncology [1.1.1, 1.1.2]. Therapeutic strategies targeting bLeY include monoclonal antibodies and antibody-drug conjugates (ADCs) like GNX1021, which are designed to induce immune-mediated destruction or deliver potent cytotoxic agents directly to tumor cells [1.4.1, 1.4.4]. A significant hurdle in the clinical development of bLeY-targeted therapies is managing "on-target, off-tumor" toxicities, particularly in the gastrointestinal system, and ensuring high specificity to avoid cross-reactivity with related glycans such as Lewis X or Lewis B [1.1.1, 1.2.2]. Recent advancements, such as protease-activated antibodies and high-affinity ADCs, aim to improve the therapeutic window for targeting this glycan in advanced cancers [1.1.1, 1.4.1].

Other names

Lewis Y antigenCD174Branched Lewis B/YbLeB/YDifucosylated tetrasaccharideLewis Y carbohydrate antigen

Antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), direct induction of apoptosis, and targeted delivery of cytotoxic payloads via antibody-drug conjugates (ADCs).