Mucin 1, cell surface associated (Tn-glycosylated) (Tn-MUC1)

Tn-MUC1 is a tumor-specific glycoform of Mucin 1 (MUC1), a large transmembrane glycoprotein that is normally heavily O-glycosylated and expressed on the apical surface of epithelial cells (UniProt: P15941). In various adenocarcinomas, the O-glycosylation pathway is disrupted, leading to the exposure of the Tn antigen (N-acetylgalactosamine) on the MUC1 protein backbone, creating a unique neoantigenic glycopeptide epitope (PubMed: 26898879). This target is highly prevalent in solid tumors such as breast, pancreatic, and ovarian cancers, where it contributes to tumor growth, metastasis, and immune suppression (PubMed: 30104341). Therapeutic strategies, most notably Chimeric Antigen Receptor (CAR) T-cell therapies, utilize engineered T-cells to recognize and bind this specific epitope using scFvs derived from antibodies like 5E5 (PubMed: 26898879). Upon binding to Tn-MUC1, these CAR-T cells are activated to eliminate malignant cells through the release of cytotoxic cytokines and granzymes (ClinicalTrials.gov: NCT04025216).

Other names

Tn-MUC1MUC1-TnTumor-associated Mucin 1CD227GalNAc-MUC1Mucin-1

Chimeric Antigen Receptor (CAR) T-cells engineered to express a single-chain variable fragment (scFv) specific for the Tn-glycopeptide epitope of MUC1 bind to the target on tumor cells, leading to T-cell activation, cytokine release, and direct cytotoxic killing of the cancer cell (PubMed: 26898879).