Biologic medicines, including monoclonal antibodies, are increasingly used to treat cancer, autoimmune and inflammatory diseases in women of reproductive age. However, many therapeutic IgG antibodies can cross the placenta and reach the developing fetus, creating challenges when these treatments are needed during pregnancy.
Researchers now uncovered an important mechanism that may help reduce fetal exposure to these medicines. The study found that the placenta can distinguish between IgG antibodies and albumin, despite both proteins being recognised by the neonatal Fc receptor (FcRn).
FcRn has an important role in extending the lifespan of proteins in the bloodstream. It binds both IgG and albumin and protects them from degradation in many tissues. However, the researchers found that placental FcRn preferentially transports IgG across the placenta while largely preventing albumin from crossing.
The team investigated this mechanism using conventional and genetically humanised mouse models, as well as an ex vivo human placental perfusion system using placentas collected after delivery. Across these models, IgG was efficiently transported to the fetal side, whereas albumin showed very limited transfer.
The researchers then asked whether this difference could be exploited to develop biologic medicines that remain in the mother’s circulation for longer while reaching the fetus to a lesser extent.
They found that attaching albumin to therapeutic IgG antibodies substantially reduced their placental transport while retaining the ability to interact with FcRn and achieve an extended circulating half-life. The team also developed antibody fragments fused to an engineered albumin variant, known as QMP, which was designed to optimise FcRn interactions.
This suggests that placental transfer and drug persistence could potentially be tuned through protein engineering, rather than relying solely on modifying treatment decisions once pregnancy occurs.
The concept was further tested in a mouse model of fetal and neonatal alloimmune thrombocytopenia (FNAIT), a pregnancy complication in which maternal antibodies attack fetal platelets. The engineered antibodies produced substantially lower fetal exposure and reduced associated effects in the offspring.
The findings provide a potential new strategy for designing biologic therapies for people who may become pregnant or require treatment during pregnancy. Rather than simply determining whether an existing antibody is sufficiently safe to use during pregnancy, future therapies could potentially be engineered from the outset to maintain prolonged activity in the mother while limiting placental transfer.
Importantly, these findings are still preclinical and do not establish the safety of engineered biologics in human pregnancies. However, they reveal an unexpected degree of selectivity in placental FcRn biology and provide a promising framework for developing long-acting biologic medicines with reduced fetal exposure.
The placenta is not simply a passive barrier to therapeutic antibodies. Understanding how it selectively handles FcRn-binding proteins could allow researchers to design biologics that retain their therapeutic benefits while minimising exposure of the developing fetus.
Journal article: Nilsen J, et al. 2026. Fusion of IgG antibodies to albumin inhibits transport across the placenta. Science Immunology.
Summary by Stefan Botha
