Terminal N-acetylgalactosamine-containing glycans (GalNAc-glycans)

Terminal N-acetylgalactosamine (GalNAc)-containing glycans are carbohydrate structures characterized by a GalNAc residue at the non-reducing terminus of an oligosaccharide chain. In human physiology, these glycans are most prominently represented by the Tn antigen (GalNAcα1-Ser/Thr), which is a fundamental precursor in the O-glycosylation pathway (Frontiers in Immunology, 2023). While typically extended into complex branched structures in healthy cells, these glycans remain truncated and exposed in over 80% of human carcinomas due to defective glycosylation machinery, such as mutations in the COSMC chaperone (MDPI, 2021). This exposure renders them potent tumor-associated carbohydrate antigens (TACAs) that are expressed in malignancies including breast, colon, and lung cancers (NIH, 2020). Consequently, they are targeted by various immunotherapeutic strategies, such as monoclonal antibodies like Gatipotuzumab and CAR-T cells (e.g., CART-TnMUC1), to induce selective tumor cell death (Frontiers in Immunology, 2023). Furthermore, terminal GalNAc residues serve as the primary ligand for the asialoglycoprotein receptor (ASGPR) in the liver, a biological interaction that is extensively utilized for the targeted delivery of therapeutic oligonucleotides like Givosiran and Inclisiran (NIH, 2021). Beyond oncology, aberrant GalNAc-containing glycans are implicated in the pathogenesis of IgA nephropathy and play roles in immune evasion by binding to inhibitory lectins like Macrophage Galactose-specific Lectin (MGL) on myeloid cells (SciSpace, 2022).

Other names

Tn antigenGalNAc-terminated glycansTumor-associated carbohydrate antigensCD175Sialyl-Tn antigenCD175s

Binding to tumor-associated carbohydrate antigens to induce immune-mediated cell death via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or direct T-cell cytotoxicity.