Quantifying the Effect of Antibody N-Glycosylation on Innate Immune Functions: Design Implications for Therapeutic Antibodies
Mammalian Synthetic Biology Workshop
Saturday, May 5, 2018 - 5:30pm to 6:30pm
Accumulating evidence suggests that patterns of N-linked glycosylation in the Fc domain of mAbs play a key role in regulating their effector functions. However, a systematic and quantitative understanding of how the complex patterns of Fc glycans control distinct immune effector mechanisms in tumor cells is lacking. A modeling framework, consisting of a system of ordinary differential equations, was developed to model the various combinations of binding of mAbs to the tumor cell antigens and the multiple Fc receptors on immune cells. The developed model recapitulates the effect of N-glycosylation by modifying kinetic binding affinities to Fc receptors. The parameters of the model were estimated using information from the literature as well as fitting to the data from preliminary experiments. Future experiments will test a representative panel of differently glycosylated synthetic cetuximab in a co-culture of colon cancer cell lines and a number of innate immune cells in vitro. This model will be able to predict the effect of N-glycosylation on the immune effector functions and offer engineering insights for enhancing mAb therapeutics.