The Jackson Laboratory, a global leader in mammalian cancer genetics modeling and education and human genomics, demonstrated that the albumin-based therapeutic, Tanzeum, had a six-fold increase in half-life in humanized FcRn mice with mouse albumin knocked out compared to when mouse albumin is present. The albumin knockout mice are a superior platform for pharmacokinetic (PK) and pharmacodynamic (PD) studies of albumin-based therapeutics. JAX will be at the AAI Annual Meeting booth #2315 to showcase these findings from May 13-17.
The study performed by The Jackson Laboratory In Vivo Pharmacology team demonstrated an increase in the half-life of Tanzeum, an albumin-based therapeutic, from 1.5 days to 9.4 days when using humanized FcRn Mice with mouse albumin knocked out. Without FcRn, Tanzeum only has a half-life of 0.6 days, which is expected based on previous data where human albumin had a half-life of 13.6 days in the albumin knockout compared to 3.6 days when mouse albumin is present.
“We are very excited to share our findings with the research community as albumin-based therapies are proving to be an effective treatment for diabetes, cancer, rheumatoid arthritis, and hemophilia,” stated Cat Lutz, Senior Research Scientist at The Jackson Laboratory. She added, “In the presence of mouse albumin, there is rapid clearance of albumin-based therapeutics from circulation preventing PK and PD analysis. Our data demonstrates the humanized FcRn models broad capabilities for evaluating the pharmacokinetics, bioavailability, and efficacy of therapeutic monoclonal antibodies and albumin-based therapeutics in vivo.”
In standard FcRn strains, mouse albumin competes with the therapeutic and inhibits PK and PD analysis due to its strong affinity for human FcRn. However, when albumin is knocked out in humanized FcRn mice, there is no competition and therefore these mice are the most clinically relevant models as they better recapitulate PK and PD dynamics seen in humans and enable researchers to quickly evaluate the half-life of albumin-engineered therapies.
The Jackson Laboratory has developed several unique mouse models that are deficient in murine FcRn and instead express human FcRn receptors coded by the FCGRT gene. These models are superior tool for the development of IgG and albumin-based therapeutics providing relevant translational data for preclinical pharamacokinetics and efficacy studies.
The Jackson Laboratory is a global leader in mammalian cancer genetics modeling and education, and has been a driving force supporting oncology research and discovery for over 85 years. The Laboratory is using the latest research methods and tools to investigate a variety of cancers, including breast, lung, brain, gastric and blood. Its recently created Jackson Laboratory for Genomic Medicine in Farmington, Connecticut will deepen its cancer research programs, accelerating the discovery of precise genomic medical solutions for disease.
Additional information is available on jax.org.