Cell surface glycans

Cell surface glycans, which comprise the glycocalyx, are complex carbohydrate chains covalently linked to proteins (glycoproteins) and lipids (glycolipids) on the outer leaflet of the plasma membrane (Varki A, Glycobiology, 2017). These structures are essential for mediating critical biological processes, including cell-cell recognition, adhesion, and the modulation of signal transduction pathways (Pinho SS & Reis CA, Nature Reviews Cancer, 2015). In many diseases, particularly cancer, the glycosylation machinery is dysregulated, leading to the expression of tumor-associated carbohydrate antigens (TACAs) such as GD2, Sialyl-Lewis X, and Globo H (Munkley J & Elliott DJ, Int J Mol Sci, 2016). These altered glycan profiles contribute to tumor progression, metastasis, and immune evasion by interacting with receptors like Siglecs and selectins. Consequently, cell surface glycans have become significant therapeutic targets for monoclonal antibodies, CAR-T cells, and glycomimetic drugs designed to disrupt pathological interactions or induce targeted cell lysis (Zhou X & Wang LX, Trends in Glycoscience and Glycotechnology, 2019).

Other names

GlycocalyxCell surface carbohydratesTumor-associated carbohydrate antigensTACAsSurface oligosaccharides

Monoclonal antibodies targeting cell surface glycans primarily act through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to eliminate target cells (Pinho SS & Reis CA, Nature Reviews Cancer, 2015). Additionally, glycomimetic small molecules and antibodies can function by competitively inhibiting the binding of glycans to their cognate receptors, such as selectins or Siglecs, thereby disrupting cell adhesion, migration, and immune evasion mechanisms (Varki A, Glycobiology, 2017).