Cancer cells undergo dramatic changes in carbohydrate expression during the onset and progression of disease. Detection of these changes is essential for understanding their basic biology as well as for monitoring changes for diagnostic purposes. Carbohydrate expression is monitored almost exclusively with anti-carbohydrate antibodies and lectins. In addition, anti-carbohydrate antibodies and lectins can be used to target tumors. For these proteins to provide accurate information on the expression of carbohydrate tumor antigens or to reliably target tumors, they must bind specifically to a particular carbohydrate of interest. Unfortunately, analysis of specificity has been difficult with conventional tools and most antibodies and lectins have not been fully characterized. In spite of the lack of information, many of the antibodies and lectins are thought to be specific and conclusions regarding carbohydrate expression are made based on this perception. We have used a carbohydrate microarray to evaluate the specificity of commonly used anti-carbohydrate antibodies and lectins and found that many have specificity problems. We are using carbohydrate microarray technology to determine which antibodies are unreliable and to develop new antibodies/lectins with improved specificity. In addition, we are using the microarray to identify carbohydrate-binding proteins that interact with carbohydrate tumor antigens.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010740-01
Application #
7338815
Study Section
(LMC)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Gildersleeve, Jeffrey C; Wang, Baomei; Achilefu, Samuel et al. (2012) Glycan array analysis of the antigen repertoire targeted by tumor-binding antibodies. Bioorg Med Chem Lett 22:6839-43
Oyelaran, Oyindasola; McShane, Lisa M; Dodd, Lori et al. (2009) Profiling human serum antibodies with a carbohydrate antigen microarray. J Proteome Res 8:4301-10
Manimala, Joseph C; Roach, Timothy A; Li, Zhitao et al. (2007) High-throughput carbohydrate microarray profiling of 27 antibodies demonstrates widespread specificity problems. Glycobiology 17:17C-23C
Manimala, Joseph C; Roach, Timothy A; Li, Zhitao et al. (2006) High-throughput carbohydrate microarray analysis of 24 lectins. Angew Chem Int Ed Engl 45:3607-10