Tn-glycoform of mucin 1 (Tn-MUC1)

The **Tn-glycoform of mucin 1** (Tn-MUC1) is a tumor-associated variant of the transmembrane glycoprotein MUC1, characterized by the presence of the Tn antigen (α-GalNAc-O-Ser/Thr) as a result of aberrant O-glycosylation in cancer cells[1][4]. MUC1 is normally a heavily glycosylated mucin found on the apical surface of epithelial cells where it lubricates and protects tissues, participates in cell signaling, and mediates cell adhesion[1][2][7]. In cancer, abnormal glycosylation leads to exposure of short O-glycan structures, particularly the Tn antigen, generating neoepitopes highly immunogenic and almost exclusively found on malignant cells[1][4][6]. Tn-MUC1 plays a role in tumor progression, immune evasion, and metastasis, making it an attractive target for immunotherapies such as CAR-T cells and antibody-based strategies[4][1]. Its selective expression on tumor cells, involvement in cancer biology, and accessibility on the cell surface highlight its utility both as a therapeutic target and a biomarker for cancer diagnosis and treatment monitoring[1][6]. Targeting this glycoform presents challenges, including heterogeneity of glycosylation in different tumors, risk of toxicity to normal tissues, and presence of soluble antigen in circulation acting as a barrier to effective antibody therapy[1][4].

Other names

MUC1-TnTn-MUC1Tn-glycosylated MUC1tumor-associated MUC1 Tn variantcancer-associated Tn-MUC1

Antibody-dependent cellular cytotoxicity (ADCC) (for monoclonal antibodies) Direct recognition and killing by CAR-T cells specific for Tn-MUC1 glycoepitope Targeting of aberrant glycoepitopes on tumor cells leading to immune-mediated clearance