Sialyl-Tn antigen (STn) on Mucin 1 (MUC1) and related mucins (STn-MUC1)

Sialyl-Tn (STn) is a truncated O-glycan consisting of a sialic acid residue alpha-2,6-linked to N-acetylgalactosamine (GalNAc), which is covalently attached to serine or threonine residues on proteins (Munkley, J., 2016, Int. J. Mol. Sci.). In healthy tissues, O-glycans are typically elongated into complex branched structures, but in many adenocarcinomas, the overexpression of the sialyltransferase ST6GalNAc-I leads to the premature termination of glycan chains, resulting in the high expression of the STn epitope on mucins like MUC1, MUC2, and MUC16 (Burchell, J.M., et al., 2018, Glycobiology). This tumor-associated carbohydrate antigen (TACA) plays a critical role in cancer progression by promoting cell migration, invasion, and immune evasion, specifically by interacting with inhibitory Siglec receptors on immune cells (Beatson, R., et al., 2016, OncoImmunology). Because STn is highly tumor-specific and largely absent in normal adult tissues, it has been a major target for therapeutic development, including the STn-KLH vaccine (Theratope) and glyco-specific monoclonal antibodies like Gatipotuzumab (Holmberg, L.A., & Sandmaier, B.M., 2001, Expert Opin. Biol. Ther.). These therapies aim to exploit the unique glycosylation patterns of cancer cells to induce targeted immune responses or deliver cytotoxic agents directly to the tumor (Pinho, S.S., & Reis, C.A., 2015, Nat. Rev. Cancer).

Other names

STnsTnCD175sSialyl-Tn epitopeNeu5Ac-alpha2,6-GalNAc-alpha-Ser/ThrTAG-72 (Tumor-associated glycoprotein 72)

Active immunotherapy via carbohydrate-conjugate vaccines; passive immunotherapy via monoclonal antibodies targeting glyco-epitopes; antibody-dependent cellular cytotoxicity (ADCC); complement-dependent cytotoxicity (CDC).