Tn and Sialyl-Tn carbohydrate antigens (Tn and sTn)

Tn and Sialyl-Tn (sTn) are truncated O-glycan structures that serve as prominent tumor-associated carbohydrate antigens (TACAs). In normal cells, O-glycan chains are extended into complex, branched structures; however, in many cancers, the glycosylation process is disrupted—often due to the downregulation of the molecular chaperone Cosmc or the upregulation of sialyltransferases like ST6GalNAc-I—leading to the premature termination of these chains (Pinho & Reis, 2015). The Tn antigen consists of a single N-acetylgalactosamine (GalNAc) residue linked to serine or threonine, while the sTn antigen features an additional sialic acid residue (Beatson et al., 2016). These antigens are overexpressed on various tumor-associated glycoproteins, most notably MUC1 and TAG-72, across a wide range of epithelial cancers including breast, colorectal, and ovarian malignancies (Ju et al., 2011). Because of their high tumor specificity and role in promoting metastasis and immune evasion, Tn and sTn are major targets for various therapeutic strategies, including monoclonal antibodies, antibody-drug conjugates (ADCs), carbohydrate-based vaccines, and CAR-T cell therapies (Miles et al., 2004). These truncated glycans contribute to the oncogenic phenotype by altering cell-cell interactions and shielding the tumor from immune recognition. Therapeutic development has focused on overcoming the low immunogenicity of these carbohydrates through conjugation to carrier proteins or the engineering of high-affinity synthetic binders.

Other names

Tn antigenSialyl-Tn antigensTnCD175CD175sGalNAc-Ser/ThrNeu5Ac-alpha2,6-GalNAc-alpha-Ser/ThrTAG-72 (Sialyl-Tn carrier)Tumor-associated O-glycansTACA

Targeting of truncated O-glycans via monoclonal antibodies, vaccines, or CAR-T cells to induce immune-mediated cytotoxicity (ADCC, CDC) or T-cell activation against tumor cells (Beatson et al., 2016; Pinho & Reis, 2015).