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University of Wisconsin-Madison

Pharm Sci Seminar – Dr. Lai-Xi Wang

March

10,

2017

Lai-Xi Wang, Ph.D., Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland (host:  Prof. Jiaoyang Jiang)

Chemoenzymatic Fc Glycan Engineering for Modulating Antibody’s Effector Functions

Monoclonal antibodies (mAbs) are an important class of therapeutic proteins widely used for the treatment of cancer, inflammation, and infectious diseases.  All IgG type antibodies carry a bi-antennary complex type N-glycan at the Asn-297 site of the Fc domain, the fine structures of the Fc glycans have been shown to be critical for the effector functions of antibodies, including the antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity, and anti-inflammatory activity.  Nevertheless, most of monoclonal antibodies on the market are produced as mixtures of glycoforms that are not optimal for their therapeutic efficacy, and controlling glycosylation to a defined homogeneous status in protein production remains a challenging task in biotech and pharmaceutical industry.  This presentation describes an enzyme-based glycosylation remodeling method for site-specific glycoengineering of antibodies, which involves an enzymatic deglycosylation and an enzymatic en bloc glycan transfer step.  A remarkable site-selectivity in glycan remodeling was achieved by taking advantage of the substrate specificity of a handful of endoglycosidases and their mutants.  The combined use of the enzyme specificity permits site-selective introduction of different glycans at different sites (Fab and Fc) in a given antibody, which has been hitherto difficult to achieve by glycoengineering at a genetic level.  Examples for glycoengineering of several therapeutic monoclonal antibodies, including rituximab and herceptin for improving their effector functions will be provided.

Room 2006 Rennebohm Hall

 

Date
Friday, March 10, 2017
Time
3:30 PM – 4:30 PM
Location

2006 Rennebohm Hall

Madison, WI 53705