Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection

Glycobiology. 2023 Aug 14;33(7):567-578. doi: 10.1093/glycob/cwad035.

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.

Keywords: Tn antigen; antibody; glycoprotein; microarrays; tumor-specific carbohydrate antigen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Tumor-Associated, Carbohydrate*
  • Biomarkers, Tumor
  • Carcinoma*
  • Cell Line
  • Glycoproteins
  • Glycosylation
  • Humans
  • Mice

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Glycoproteins
  • Biomarkers, Tumor