Truncated Core 1 O-glycan (Tn/STn antigen)

Truncated Core 1 O-glycans, primarily represented by the Tn (GalNAc-Ser/Thr) and Sialyl-Tn (STn) antigens, are aberrant carbohydrate structures that arise during the early stages of O-linked glycosylation. In healthy tissues, these precursor structures are rapidly elongated into complex, branched O-glycans by enzymes such as C1GALT1 and its essential molecular chaperone, Cosmc (Ju et al., 2008, Nature). However, in many epithelial cancers, the loss of Cosmc function or dysregulation of glycosyltransferases leads to the premature termination of glycan chains, resulting in the dense expression of these truncated structures on the cell surface (Pinho & Reis, 2015, Nature Reviews Cancer). These antigens are frequently found on mucins like MUC1 and MUC16, where they alter protein conformation and promote oncogenic signaling and metastasis. Because truncated O-glycans are virtually absent in normal adult tissues but highly prevalent in various adenocarcinomas, they serve as highly specific targets for immunotherapy. Therapeutic strategies include monoclonal antibodies like Gatipotuzumab, which targets the Tn-MUC1 epitope, and glycan-based vaccines like Theratope (Beatson et al., 2016, PLOS ONE). Current research also explores CAR-T cells engineered to recognize these glycopeptide motifs to induce potent and selective tumor cell lysis.

Other names

Tn antigenSialyl-Tn antigenSTnThomsen-Friedenreich antigenTF antigenT antigenGalNAc-alpha-Ser/ThrTumor-associated carbohydrate antigenTACA

Antibody-dependent cellular cytotoxicity (ADCC), T-cell mediated cytotoxicity, Complement-dependent cytotoxicity (CDC), Vaccine-induced humoral immune response