Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection

作者：Kudelka, Matthew R.; Gu, Wei; Matsumoto, Yasuyuki; Ju, Tongzhong; Barnes II, Richard H.; Kardish, Robert J.; Heimburg-Molinaro, Jamie; Lehoux, Sylvain; Zeng, Junwei; Cohen, Cynthia; Robinson, Brian S.; Shah, Kinjal S.; Chaikof, Elliot L.; Stowell, Sean R.; Cummings, Richard D.^*

来源：Glycobiology, 2023, 33(7): 567-578.

DOI：10.1093/glycob/cwad035

• antibody
• glycoprotein
• microarrays
• Tn antigen
• tumor-specific carbohydrate antigen

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. @@@ We have developed a novel anti-Tn antigen-based immuno-platform to detect Tn+ glycoproteins expressed by tumor cells as a single reagent to promote early universal cancer detection.

• 单位
  广东省人民医院; 南方医科大学