Truncated O-glycans (TACA)

Truncated O-glycans are a class of tumor-associated carbohydrate antigens (TACAs) that arise from the premature termination of O-linked glycosylation pathways in malignant cells (Ju et al., 2013). In healthy tissues, O-glycans are typically extended into complex branched structures; however, in many cancers, mutations or expression changes in glycosyltransferases lead to the accumulation of short, truncated structures like the Tn (GalNAc-Ser/Thr), Sialyl-Tn (STn), and Thomsen-Friedenreich (TF) antigens (Pinho & Reis, 2015). These truncated glycans are highly specific to tumor cells and play critical roles in promoting oncogenic signaling, cell invasion, and immune evasion by interacting with various lectins such as MGL or Siglecs (Varki et al., 2017). Because of their high tumor specificity and presence on the cell surface, they are prime targets for immunotherapy, including monoclonal antibodies, cancer vaccines, and chimeric antigen receptor (CAR) T-cell therapies (Posey et al., 2016). Targeting these glycans aims to induce immune-mediated destruction of cancer cells while sparing normal tissues that lack these truncated motifs. Clinical development has focused on vaccines like Theratope and glyco-specific antibodies like Gatipotuzumab to exploit these neoantigens.

Other names

Tn antigenSialyl-Tn antigenSTnThomsen-Friedenreich antigenTF antigenTumor-associated carbohydrate antigensTACACD175CD175sCD176

Targeted immune-mediated cell lysis via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or direct T-cell cytotoxicity (Posey et al., 2016).