Thomsen-nouveau antigen on Mucin-1 (Tn-MUC1)

Thomsen-nouveau antigen on Mucin-1 (Tn-MUC1) is a tumor-associated glycoform of the Mucin-1 protein, characterized by the presence of the Tn antigen (N-acetylgalactosamine O-linked to serine or threonine) due to aberrant O-glycosylation in cancer cells (NIH, 2021; Posey et al., 2016). In healthy tissues, Mucin-1 is a heavily glycosylated transmembrane protein that provides a physical barrier and lubrication on epithelial surfaces, with its protein core masked by long, branched carbohydrate chains (Frontiers in Oncology, 2019; NIH, 2021). In malignant cells, the loss of the molecular chaperone COSMC or alterations in glycosyltransferases lead to the production of truncated glycans, exposing the Tn-MUC1 neoepitope which is highly specific to tumors (Cancer.gov, 2021; ESMO, 2025). This target is widely expressed in epithelial cancers such as breast, ovarian, pancreatic, and lung cancers, where it promotes oncogenic signaling, cell proliferation, and metastasis (AACR, 2020; NIH, 2021). Therapeutic approaches targeting Tn-MUC1 include monoclonal antibodies like Gatipotuzumab, antibody-drug conjugates such as DS-3939, and CAR-T cell therapies, which aim to exploit the high tumor-selectivity of the glycopeptide motif (ASCO, 2021; ESMO, 2025). While generally well-tolerated due to low expression in normal tissues, safety considerations include potential on-target off-tumor effects and specific toxicities like interstitial lung disease associated with certain drug payloads (ESMO, 2025; NIH, 2025).

Other names

Tn-MUC1MUC1-TnTnMUC1GalNAc-Ser/Thr Mucin-1Tumor-associated Mucin-1TA-MUC1CD227

Targeted immunotherapy utilizing monoclonal antibodies, antibody-drug conjugates, and CAR-T cells to recognize the aberrant Tn-MUC1 glycoform, leading to tumor cell death via antibody-dependent cellular cytotoxicity (ADCC), cytotoxic payload delivery, or T-cell mediated lysis.