Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection.

Kudelka MR, Gu W, Matsumoto Y, Ju T, Barnes RH Ii, Kardish RJ, Heimburg-Molinaro J, Lehoux S, Zeng J, Cohen C, et al. Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection.. Glycobiology. 2023;33(7):567–578.

Abstract

There is an urgent need to develop new tumor biomarkers for early cancer detection, but the variability of tumor-derived antigens has been a limitation. Here we demonstrate a novel anti-Tn antibody microarray platform to detect Tn+ glycoproteins, a near universal antigen in carcinoma-derived glycoproteins, for broad detection of cancer. The platform uses a specific recombinant IgG1 to the Tn antigen (CD175) as a capture reagent and a recombinant IgM to the Tn antigen as a detecting reagent. These reagents were validated by immunohistochemistry in recognizing the Tn antigen using hundreds of human tumor specimens. Using this approach, we could detect Tn+ glycoproteins at subnanogram levels using cell lines and culture media, serum, and stool samples from mice engineered to express the Tn antigen in intestinal epithelial cells. The development of a general cancer detection platform using recombinant antibodies for detection of altered tumor glycoproteins expressing a unique antigen could have a significant impact on cancer detection and monitoring.

Last updated on 11/02/2023
PubMed