Tn antigen (Tn) (Tn)

The Tn antigen (GalNAc-alpha-O-Ser/Thr) is a truncated O-glycan consisting of a single N-acetylgalactosamine residue alpha-linked to serine or threonine residues on proteins (Springer, 1984, Science). Under normal physiological conditions, this precursor is rapidly extended by glycosyltransferases into more complex structures; however, in many cancers, this process is disrupted—often due to the loss of the Cosmc chaperone or T-synthase activity—leading to the dense expression of Tn on the cell surface (Ju et al., 2014, Nature Communications). As a prominent tumor-associated carbohydrate antigen (TACA), it is found in a high percentage of epithelial cancers, including breast, colon, and prostate, while remaining virtually absent in healthy tissues, making it an exceptionally specific biomarker and therapeutic target (Heimburg-Molinaro et al., 2011, Vaccine). Current clinical strategies targeting the Tn antigen include monoclonal antibodies like Gatipotuzumab, glycopeptide-based vaccines like MAG-Tn3, and chimeric antigen receptor (CAR) T-cell therapies designed to induce immune-mediated destruction of malignant cells (Posey et al., 2016, Immunity). Beyond its role as a target, Tn expression is associated with increased tumor invasiveness, metastasis, and poor prognosis, as it can modulate cell-cell adhesion and help the tumor evade immune detection (Mazal et al., 2013, Histology and Histopathology).

Other names

Thomsen-nouveau antigenCD175GalNAc-alpha-Ser/ThrGalNAc-alpha-O-Ser/ThrTn glycan

The primary mechanism of action involves the specific recognition of the Tn glycan or Tn-glycopeptide neoepitopes on tumor cells by therapeutic agents, which then trigger immune-mediated destruction through antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or direct T-cell mediated lysis (Posey et al., 2016, Immunity; Heimburg-Molinaro et al., 2011, Vaccine).