Tn-glycosylated protein (Tn antigen)

Tn-glycosylated proteins are a class of glycoproteins defined by the presence of the Tn antigen (GalNAcα1-O-Ser/Thr), a truncated O-glycan that is a well-recognized tumor-associated carbohydrate antigen (TACA) (Ju et al., 2014, Nature Reviews Cancer). Under normal physiological conditions, the Tn antigen is a transient biosynthetic intermediate that is rapidly elongated into complex O-glycans; however, in many epithelial cancers, this process is disrupted by mutations in the molecular chaperone Cosmc or the dysregulation of glycosyltransferases (Schjoldager et al., 2020, Nature Reviews Molecular Cell Biology). This results in the dense expression of Tn-glycosylated proteins, such as MUC1, on the surface of malignant cells, where they facilitate tumor invasion, metastasis, and immune evasion (Beatson et al., 2016, PLoS One). Because the Tn antigen is virtually absent in healthy adult tissues but highly prevalent in various solid tumors, it is an ideal target for precision immunotherapy (Posey et al., 2016, Immunity). Current therapeutic approaches include monoclonal antibodies, such as 5E5, and CAR-T cell therapies like CART-TnMUC1, which are designed to recognize the unique glycopeptide neoepitopes formed by the truncated sugar (Mazal et al., 2022, Frontiers in Oncology). These therapies aim to exploit the high tumor specificity of the Tn antigen to minimize off-target effects while inducing potent anti-tumor immune responses.

Other names

Tn antigenGalNAc-alpha-Ser/ThrCD175Tumor-associated carbohydrate antigenTACAN-acetylgalactosamine-serine/threonine

Targeted binding to truncated O-glycan epitopes on tumor cells to trigger immune-mediated destruction via ADCC, T-cell activation, or vaccine-induced antibody production.