Carbohydrate-binding antibodies are used extensively for basic research and are useful as diagnostic and therapeutic agents. They are especially useful in the field of cancer. Cancer cells undergo dramatic changes in carbohydrate expression during the onset and progression of disease. As a result, there has been considerable interest in understanding why these changes occur, how they contribute to the disease, and exploiting these changes for clinical use. For example, Unituxin (dinituximab) is an FDA approved monoclonal antibody that targets the tumor associated carbohydrate GD2 and is used to treat children with neuroblastoma. Unfortunately, there are very few good monoclonal antibodies to carbohydrates. The lack of high quality antibodies is a major barrier for the field. We are taking a multi-pronged approach to help alleviate this problem. First, we use our glycan microarray to evaluate the selectivities of existing antibodies to carbohydrates. This information is crucial for selecting the right antibody for a particular application and interpreting results. Second, we have developed a database of antibodies to carbohydrates (Database of Anti-Glycan Reagents; DAGR) that can be used to find antibodies and information about those antibodies. Third, we are studying the mechanisms by which antibodies to carbohydrates are produced in mammals. Fourth, we are using our glycan microarray to discover and engineer new antibodies to carbohydrates

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010740-14
Application #
10014431
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Kumar, Pardeep; Kuhlmann, F Matthew; Chakraborty, Subhra et al. (2018) Enterotoxigenic Escherichia coli-blood group A interactions intensify diarrheal severity. J Clin Invest 128:3298-3311
Lubkowski, Jacek; Durbin, Sarah V; Silva, Mariana C C et al. (2017) Structural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growth. FEBS J 284:429-450
Gibadullin, Ruslan; Farnsworth, David Wayne; Barchi Jr, Joseph J et al. (2017) GalNAc-Tyrosine Is a Ligand of Plant Lectins, Antibodies, and Human and Murine Macrophage Galactose-Type Lectins. ACS Chem Biol 12:2172-2182
Sterner, Eric; Peach, Megan L; Nicklaus, Marc C et al. (2017) Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies. Cell Rep 20:1681-1691
Sterner, Eric; Flanagan, Natalie; Gildersleeve, Jeffrey C (2016) Perspectives on Anti-Glycan Antibodies Gleaned from Development of a Community Resource Database. ACS Chem Biol 11:1773-83
Gildersleeve, Jeffrey C; Wright, Whitney Shea (2016) Diverse molecular recognition properties of blood group A binding monoclonal antibodies. Glycobiology 26:443-8
Rho, Jung-hyun; Mead, Judson R; Wright, W Shea et al. (2014) Discovery of sialyl Lewis A and Lewis X modified protein cancer biomarkers using high density antibody arrays. J Proteomics 96:291-9
Wang, Linlin; Cummings, Richard D; Smith, David F et al. (2014) Cross-platform comparison of glycan microarray formats. Glycobiology 24:507-17
Hong, Xia; Ma, Mark Z; Gildersleeve, Jeffrey C et al. (2013) Sugar-binding proteins from fish: selection of high affinity ""lambodies"" that recognize biomedically relevant glycans. ACS Chem Biol 8:152-60
Luo, Ming; Velikovsky, C Alejandro; Yang, Xinbo et al. (2013) Recognition of the Thomsen-Friedenreich pancarcinoma carbohydrate antigen by a lamprey variable lymphocyte receptor. J Biol Chem 288:23597-606

Showing the most recent 10 out of 24 publications