Tn-glycosylated Mucin 1 (Tn-MUC1)

Tn-glycosylated Mucin 1 (Tn-MUC1) is a tumor-specific glycoform of the Mucin 1 protein, a large transmembrane glycoprotein typically found on the apical surface of epithelial cells [1]. In healthy tissues, MUC1 is extensively glycosylated with long, branched carbohydrate chains that mask its protein core; however, in many cancers, this process is disrupted, resulting in the expression of truncated O-glycans such as the Tn antigen (GalNAc-O-Ser/Thr) [2]. This aberrant glycosylation creates a unique neoantigen, Tn-MUC1, which is highly overexpressed in various adenocarcinomas, including breast, pancreatic, and ovarian cancers, while remaining virtually absent in normal tissues [2, 5]. Tn-MUC1 plays a critical role in oncogenesis by promoting cell migration, invasion, and immune evasion through its interaction with various lectins and signaling molecules [5]. Because of its high tumor specificity, Tn-MUC1 is a premier target for various immunotherapeutic approaches, including monoclonal antibodies like Gatipotuzumab and vaccine candidates like MAG-Tn3 [3, 4]. These treatments aim to exploit the unique structural features of Tn-MUC1 to selectively target and destroy malignant cells while sparing healthy epithelium [2]. References: [1] UniProt P15941; [2] Beatson et al. (2016) Cancer Immunol Immunother; [3] ClinicalTrials.gov NCT01222624; [4] Sorensen et al. (2006) Glycobiology; [5] Nath & Mukherjee (2014) Trends Mol Med.

Other names

Tn-MUC1MUC1-TnTumor-associated Mucin 1GalNAc-MUC1TA-MUC1Mucin 1, cell surface associated

Binding to the tumor-specific Tn-glycosylated epitope of Mucin 1 to induce immune-mediated cell death via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or T-cell redirection.