Tn and Sialyl-Tn tumor-associated glycan antigens (Tn and STn) (Tn and STn)

Tn and Sialyl-Tn (STn) are truncated O-glycan structures that serve as prominent tumor-associated carbohydrate antigens (TACAs) (Pinho & Reis, 2015, Nature Reviews Cancer). In healthy tissues, O-glycan chains are typically elongated into complex branched structures; however, in many epithelial cancers, alterations in glycosyltransferase expression or mutations in the molecular chaperone Cosmc lead to the premature termination of glycosylation (Ju et al., 2013, Nature Reviews Cancer). This results in the exposure of the Tn antigen (GalNAc-alpha-Ser/Thr) or its sialylated derivative, STn (Neu5Ac-alpha-2,6-GalNAc-alpha-Ser/Thr), on mucin-type glycoproteins such as MUC1. These antigens are overexpressed in a wide range of carcinomas, including breast, colorectal, gastric, and ovarian cancers, where their presence often correlates with poor prognosis and increased metastatic potential. Mechanistically, these truncated glycans contribute to tumor progression by altering cell adhesion, promoting migration, and facilitating immune evasion by hindering the recognition of tumor cells by the immune system (Beatson et al., 2016, Clinical & Experimental Immunology). Because of their high tumor specificity and prevalence, Tn and STn are major targets for cancer immunotherapy, including carbohydrate-based vaccines, monoclonal antibodies, and CAR-T cell therapies (Posey et al., 2016, Immunity). Therapeutic strategies like the STn-KLH vaccine (Theratope) and Tn-MUC1 targeted CAR-T cells aim to induce immune-mediated destruction of cancer cells while sparing normal tissues that lack these truncated glycan profiles.

Other names

Tn antigenSialyl-Tn antigenSTnCD175CD175sGalNAc-alpha-Ser/ThrNeu5Ac-alpha-2,6-GalNAc-alpha-Ser/ThrTAG-72Tumor-associated glycoprotein 72

Induction of targeted immune responses against tumor-specific truncated O-glycans to facilitate antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or T-cell mediated lysis of tumor cells.