Lewis blood group antigen (Lewis a, Lewis c, and Lewis x) (Le antigens (Le^a, Le^c, Le^x))

Lewis a, Lewis c, and Lewis x glycans are a family of carbohydrate antigens belonging to the Lewis blood group system, defined by specific fucose linkages to Type 1 or Type 2 precursor oligosaccharide chains. These glycans are expressed on the surface of various cell types, including epithelial cells and leukocytes, where they play fundamental roles in cell-cell recognition, adhesion, and the recruitment of immune cells to sites of inflammation. In healthy tissues, their expression is tightly regulated; however, in many carcinomas—such as pancreatic, colorectal, and gastric cancers—these glycans are frequently overexpressed or modified into sialylated forms like sialyl-Lewis a (CA19-9) and sialyl-Lewis x. These tumor-associated carbohydrate antigens (TACAs) facilitate cancer progression by promoting metastasis through selectin-mediated adhesion and helping the tumor evade immune detection. Therapeutic strategies targeting these glycans include monoclonal antibodies like FG88.2, which are designed to induce antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) against tumor cells. Additionally, carbohydrate-based vaccines are being developed to stimulate the immune system to recognize these specific glycan signatures. Despite their potential, a major challenge in targeting Lewis antigens is their expression on some normal tissues, which necessitates high specificity to avoid off-target toxicities.

Other names

Lewis antigensCD15SSEA-1Stage-specific embryonic antigen 1Gal-GlcNAc structuresType 1 and Type 2 Lewis antigens

Antibody-dependent cellular cytotoxicity (ADCC), Complement-dependent cytotoxicity (CDC), Inhibition of cell adhesion, Blocking of selectin-ligand interactions