High-mannose Man9 glycan (Man9)

High-mannose Man9 glycans (Man9GlcNAc2) are N-linked oligosaccharides that play a critical role in the early stages of protein glycosylation within the endoplasmic reticulum (ER) (Varki et al., 2015). While typically processed into complex glycans before reaching the cell surface in healthy cells, Man9 is frequently overexpressed on the surface of various cancer cells, including those in breast and colorectal cancers, due to altered enzymatic activity or rapid protein trafficking (Wang et al., 2018). This aberrant surface expression allows Man9 to function as a tumor-associated carbohydrate antigen (TACA) that can be exploited for targeted therapy. Therapeutic strategies targeting these glycans include the use of mannose-binding lectins like Griffithsin and monoclonal antibodies such as 2G12, which was originally identified for its ability to neutralize HIV-1 by binding to similar glycan clusters on the viral envelope (Scanlan et al., 2002). These agents work by recognizing the dense presentation of mannose residues to trigger immune-mediated destruction via antibody-dependent cellular cytotoxicity (ADCC) or by blocking essential cellular interactions. However, a significant challenge in targeting Man9 is the potential for off-target effects on the high-mannose structures essential for protein folding in the ER of normal cells.

Other names

Man9GlcNAc2Oligomannose-9High-mannose N-glycanMan9-type N-glycanMan9-cluster

Targeted binding to clustered mannose residues on the cell surface or viral envelope to induce immune-mediated destruction (ADCC/CDC) or prevent viral entry.