Fusion of IgG antibodies to albumin inhibits transport across the placenta
Immunoglobulin G (IgG)-based monoclonal antibodies are effective therapies for cancer, autoimmune diseases, and migraine. However, they are actively transported across the placenta by the neonatal Fc receptor (FcRn), limiting their use during pregnancy. Using mouse models and an ex vivo human placental perfusion system, we show that although FcRn binds albumin independently of IgG, albumin is not transported to the fetus in mice or across human placental tissue. Fusion of IgG to albumin markedly reduced transplacental transport in both models while preserving the prolonged plasma half-life conferred by FcRn. Similarly, fragment antigen-binding fragments fused to engineered albumin with enhanced FcRn binding showed minimal fetal exposure. In a mouse model of fetal and neonatal alloimmune thrombocytopenia, albumin fusion of an anti-human platelet antigen IgG reduced fetal antibody transfer and attenuated thrombocytopenia in the offspring. These findings identify albumin as an attractive fusion partner for biologics intended to minimize fetal exposure during pregnancy.
Authors
- Tilman Schlothauer (ORCID: https://orcid.org/0000-0001-5844-4438)
- Jan Terje Andersen (ORCID: https://orcid.org/0000-0003-1710-1628)
- Simone Mester (ORCID: https://orcid.org/0000-0002-5751-063X)
- A. Moen
- Derry C. Roopenian (ORCID: https://orcid.org/0000-0001-8409-7214)
- Aina Karen Anthi (ORCID: https://orcid.org/0000-0002-1725-4571)
- Jeannette Nilsen (ORCID: https://orcid.org/0000-0001-7892-0892)
- Eirin Listau Bertelsen (ORCID: https://orcid.org/0000-0002-4629-0205)
- Gregory J. Christianson (ORCID: https://orcid.org/0000-0001-5532-342X)
- Kine Marita Knudsen Sand (ORCID: https://orcid.org/0000-0002-5758-1016)
- Inger Sandlie (ORCID: https://orcid.org/0009-0005-8063-0145)
- Fulgencio Ruso‐Julve (ORCID: https://orcid.org/0000-0001-6500-6807)
- Sopisa Benjakul (ORCID: https://orcid.org/0000-0003-3708-8125)
- Mari Nyquist-Andersen (ORCID: https://orcid.org/0000-0002-5248-6722)
- Nils Leitzinger
- Hana J. Al Khabbaz (ORCID: https://orcid.org/0000-0002-9051-8262)
- Lisbeth E. Knudsen (ORCID: https://orcid.org/0000-0002-9576-1202)
- Line Mathiesen (ORCID: https://orcid.org/0000-0002-3210-159X)
- Jason Cameron
- Maria Therese Ahlén (ORCID: https://orcid.org/0000-0002-3104-3818)
- Stian Foss (ORCID: https://orcid.org/0000-0001-6527-051X)
- Tor B. Stuge (ORCID: https://orcid.org/0000-0002-6933-8419)
- Marie Leangen Herigstad
- Hanna Theodora Noordzij (ORCID: https://orcid.org/0009-0001-7226-887X)
- Torleif Tollefsrud Gjølberg (ORCID: https://orcid.org/0000-0002-1719-7677)
- Oda Ottersen
- Kjell-Rune Jensen (ORCID: https://orcid.org/0009-0001-1710-0986)
- Lennart Maximilian van Ligtenberg (ORCID: https://orcid.org/0009-0007-5385-0921)
Institutions
- Roche (Switzerland) (CH)
- University of Copenhagen (DK)
- Oslo University Hospital (NO)
- University Hospital of North Norway (NO)
- University of Oslo (NO)
- Riyadh Elm University (SA)
- Jackson Laboratory (US)
- Albumedix (United Kingdom) (GB)
- UiT The Arctic University of Norway (NO)
Publication Details
- Journal
- Science Immunology
- Published
- 2026-08-14
- DOI
- https://doi.org/10.1126/sciimmunol.aee5151
- Primary Topic
- Monoclonal and Polyclonal Antibodies Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Norges Forskningsråd
- National Institutes of Health
- Helse Sør-Øst RHF