Amplified Detection of Breast Cancer Autoantibodies Using MUC1-Based Tn Antigen Mimics

In
many human carcinomas, mucin-1 (MUC1) is overexpressed and aberrantly
glycosylated, resulting in the exposure of previously hidden antigens.
This generates new patient antibody profiles that can be used in cancer
diagnosis. In the present study, we focused on the MUC1-associated
Tn antigen (α-O-GalNAc-Ser/Thr) and substituted
the GalNAc monosaccharide by a glycomimic to identify MUC1-based glycopeptides
with increased antigenicity. Two different glycopeptide libraries
presenting the natural Tn antigen or the sp2-iminosugar analogue were synthesized and evaluated with anti-MUC1
monoclonal antibodies in a microarray platform. The most promising
candidates were tested with healthy and breast cancer sera aiming
for potential autoantibody-based biomarkers. The suitability of sp2-iminosugar glycopeptides to detect anti-MUC1
antibodies was demonstrated, and serological experiments showed stage
I breast cancer autoantibodies binding with a specific unnatural glycopeptide
with almost no healthy serum interaction. These results will promote
further studies on their capabilities as early cancer biomarkers.