Tumor-associated truncated core 1 and extended core 1 O-glycans on glycoproteins (TACA)

Tumor-associated truncated core 1 and extended core 1 O-glycans, collectively known as Tumor-Associated Carbohydrate Antigens (TACAs), represent a class of aberrant post-translational modifications prevalent in epithelial cancers (Pinho & Reis, 2015, Nature Reviews Cancer). In normal physiology, O-glycans are typically extended into complex, branched chains that shield proteins and mediate healthy cell-cell interactions. In malignancy, however, the loss of the Cosmc chaperone or altered glycosyltransferase activity leads to the premature termination of these chains, exposing truncated structures like the Tn (GalNAc), Sialyl-Tn (STn), and Thomsen-Friedenreich (TF) antigens (Ju et al., 2014, Glycobiology). These glycans act as neoantigens and are involved in promoting tumor cell adhesion, invasion, and immune evasion, particularly through the recruitment of inhibitory Siglec receptors on immune cells (Beatson et al., 2016, PLOS ONE). Because these structures are highly tumor-specific, they are being utilized as targets for a variety of immunotherapies, including monoclonal antibodies, glycan-modifying enzymes, and CAR-T cells (Posey et al., 2016, Immunity). Current clinical candidates like E-602 and Gatipotuzumab aim to either remove these immunosuppressive sugars or directly kill the cells expressing them.

Other names

Tn antigenSialyl-Tn antigenSTnThomsen-Friedenreich antigenTF antigenCore 1 O-glycanTruncated O-glycansTumor-associated carbohydrate antigens (TACA)TAG-72Tumor-associated MUC1 glycans

Targeted cell depletion via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), enzymatic desialylation of the tumor surface to reverse immune suppression, and CAR-T cell-mediated direct cytotoxicity.