research interest

Title: Development of Antibody-Drug Conjugates (ADCs) for therapeutic applications.

Monoclonal antibodies (mAbs) can be used to create special delivery systems known as antibody-drug conjugates (ADCs) for highly potent and toxic drugs in targeted cancer therapy. These ADCs attach drug molecules to specific points on the mAb, either through cysteine coupling, where we alter the mAb's structure to form thioether bonds, or lysine coupling, where we connect drug molecules to amine side chains on the mAb.

However, traditional methods lack precise control because mAbs have numerous attachment points, resulting in variations in the number of drug molecules which can affect safety, effectiveness, stability, toxicity, target interactions, and pharmacokinetics. Mylotarg, the first approved ADC, faced issues due to this variability and was temporarily withdrawn from the market.

Glycoengineering offers a solution by using enzymes to add non-natural sugars and precisely attach drug molecules to create uniform ADCs. Attaching drugs to the Fc N-glycan of mAbs offers advantages: it doesn't interfere with target binding, helps maintain a balance with hydrophobic drugs, and improves precision, enhancing treatment efficacy and reducing the risk of side effects and regulatory challenges.

Key Objectives:

• Develop glycoengineered mAbs featuring terminal sialylation for improved drug conjugation.

• Investigate the site-specific drug conjugation potential at sialic acid residues in the Fc region of mAbs.

• Utilize glycoengineering techniques to elevate the efficacy of antibody-drug conjugates (ADCs). 

• Enhance ADC performance through the modification of mAb glycosylation patterns.