Mucin 1 (MUC1) extracellular tandem repeat domain (MUC1-VNTR)

Mucin 1 (MUC1) is a type I transmembrane glycoprotein characterized by a large extracellular domain containing a variable number of tandem repeats (VNTR) of 20 amino acids (UniProt P15941). In healthy epithelial tissues, this domain is extensively O-glycosylated, providing a physical barrier and lubricating the cell surface (Nath & Mukherjee, 2014). However, in over 90% of adenocarcinomas, MUC1 is overexpressed, loses its apical localization, and exhibits aberrant, truncated glycosylation within the VNTR region (Kufe, 2009). This hypoglycosylation exposes the peptide backbone and creates tumor-specific glycopeptide epitopes, such as the Tn and sialyl-Tn antigens, making the VNTR domain a highly attractive target for cancer immunotherapy (Cheever et al., 2009). Therapeutic approaches targeting this domain include cancer vaccines like Tecemotide, monoclonal antibodies such as Gatipotuzumab, and chimeric antigen receptor (CAR) T-cell therapies (ClinicalTrials.gov). Despite its promise, challenges remain regarding the potential for on-target off-tumor toxicity and the immunosuppressive nature of the tumor microenvironment.

Other names

CD227CA 15-3Polymorphic epithelial mucinPEMEpithelial membrane antigenEMAH23AGPUMKL-6MAM6Variable number tandem repeat domain of MUC1

Active and passive immunotherapy targeting tumor-associated glycopeptide epitopes within the tandem repeat domain