Tumor-associated O-glycan (Truncated and Extended Core 1) (TACA)

Truncated and extended core 1 O-glycans are aberrant carbohydrate structures found on tumor-associated glycoproteins, most notably MUC1 (Pinho & Reis, 2015). In healthy tissues, O-glycans are typically elongated into complex branched structures; however, in malignant cells, dysregulation of glycosyltransferases—such as mutations in the molecular chaperone Cosmc or overexpression of sialyltransferases—leads to the presentation of shortened structures like the Tn (GalNAc-Ser/Thr) and Sialyl-Tn (STn) antigens (Ju et al., 2014). These glycans play a critical role in promoting tumor progression by enhancing oncogenic signaling, facilitating metastasis through altered cell-cell adhesion, and contributing to immune evasion by masking peptide epitopes or interacting with inhibitory receptors on immune cells (Beatson et al., 2016). Because these truncated glycoforms are highly specific to cancerous tissues and are absent or sequestered in normal cells, they serve as attractive targets for therapeutic interventions, including monoclonal antibodies, chimeric antigen receptor (CAR) T-cells, and cancer vaccines (Posey et al., 2016). Drugs targeting these glycans aim to induce antibody-dependent cellular cytotoxicity or direct T-cell mediated destruction of tumor cells while sparing normal cells that express mature, elongated glycan chains.

Other names

Tn antigenSialyl-Tn (STn) antigenThomsen-Friedenreich (TF) antigenT-antigenTumor-associated carbohydrate antigen (TACA)MUC1-associated glycan

Antibody-dependent cellular cytotoxicity (ADCC), CAR-T cell-mediated cytotoxicity, and active immunization against tumor-specific glycoepitopes.