“Systems Analysis of Glycosylated Antibodies: Regulation, Engineering and Functions”
N-linked glycosylation is a post-translational modification that affects potency, safety, immunogenicity, immune effector functions, and clearance of various classes of therapeutic proteins including antibodies. These modifications are shaped by cellular and enzyme-mediated processes, regulated at both transcriptional and metabolic levels. Understanding how these processes operate dynamically will be vital to designing the most effective therapeutics for various treatment applications, but at the present time principled insights are limited due to the complexity of contributing factors. I will describe a systems biology approach that includes multi-dimensional omics analyses and mathematical modeling to develop a mechanistic understanding of N-glycosylation of antibodies produced during fed-batch cultures of producer cells, generating new insights that offer opportunities for more precise control of N-glycosylation. The functional role of glycosylation will then be probed in a representative study, where selective transfer of antibodies with di-galactosylated Fc-glycan profiles across the placenta from mothers to newborns is observed. This additional work can provide critical information for the design of next generation maternal vaccines engineered to elicit antibodies that will effectively enhance immunity in neonates.