Tumor-associated truncated O-glycans (TACAs)

Tumor-associated truncated O-glycans are aberrant carbohydrate structures, such as the Tn, Sialyl-Tn (STn), and Thomsen-Friedenreich (TF) antigens, that arise from the premature termination of O-glycosylation in the Golgi apparatus. In healthy cells, O-glycosylation typically proceeds to form complex, branched structures; however, in cancer, mutations or dysregulation of glycosyltransferases (e.g., ST6GalNAc-I) and chaperones (e.g., COSMC) lead to the accumulation of these immature forms on cell-surface glycoproteins like MUC1 and CD44. These antigens are virtually absent in normal adult tissues but are highly expressed in various carcinomas, where they promote tumor invasion, metastasis, and immune evasion by interacting with inhibitory receptors like Siglecs and MGL on immune cells. Their presence is a hallmark of malignancy and is strongly associated with poor patient prognosis across multiple cancer types, including breast, colorectal, and pancreatic cancers. Due to their high tumor specificity, they are being extensively explored as targets for novel immunotherapies, including monoclonal antibodies (e.g., Gatipotuzumab), therapeutic vaccines (e.g., Theratope), and chimeric antigen receptor (CAR) T-cell therapies.

Other names

Tumor-associated truncated O-glycans on cell-surface glycoproteinsTn antigen (GalNAcα-Ser/Thr)Sialyl-Tn (STn) antigen (Neu5Acα2-6GalNAcα-Ser/Thr)Thomsen-Friedenreich (TF) antigen (Galβ1-3GalNAcα-Ser/Thr)T antigenCD175CD175sCD176Tumor-associated carbohydrate antigens

Targeted immunotherapy via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC); induction of humoral and cellular immune responses through glycopeptide vaccines; blocking of immunosuppressive glycan-lectin interactions (e.g., Siglec-15/STn axis); and direct tumor cell lysis by chimeric antigen receptor (CAR) T-cells or antibody-drug conjugates (ADCs).