Speaker
Description
Monoclonal antibody (mAb) therapies, although widely established in cancer treatment, are increasingly being developed and repurposed for the long term management of chronic autoimmune and inflammatory conditions such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Many of these conditions disproportionately affect women, raising important questions about fetal exposure when mAbs are taken during pregnancy, whether inadvertently or as part of maternal disease control. Most therapeutic mAbs are engineered from human immunoglobulin G (IgG) and therefore interact with the same pathways as endogenous IgG antibodies. This includes the pathways which allow maternal IgGs to pass to the fetus through the placenta. In this work, we present a mathematical model of mAb transport across the human placenta, calibrated using experimental data from ex vivo placental perfusion studies. The human placenta contains two circulations, maternal and fetal, that come into close contact to allow for the transfer of oxygen and nutrients, however, are anatomically separate. Using ODEs we model the placental compartments, FcRn expression, and associated transport processes to explore how these factors influence fetal exposure to mAbs. Understanding placental mAb transfer is essential for informing regulatory decisions on mAb use in pregnancy, and our model provides a mechanistic framework to predict fetal exposure and quantify risks.
