Jax Labs eBook - 33

IMPACTFUL SOLUTIONS CREATE INNOVATIVE SCIENCE | QUICK FACTS

WHAT KINDS OF IN VIVO MODELS HELP MODEL HALF-LIFE FOR
HUMAN THERAPEUTICS?

Getty Images, Tetra Images

Standard or wild type mice can be relatively inexpensive in vivo models. However,
human IgG (and by extension, human Fc-conjugates) binds to mouse FcRn through
different amino acid residues resulting in PK data that doesn't correlate well with
human data. Thus, when standard mice are used, half-life outcomes can be highly
variable, and clinically-relevant data is not produced.
Alternatively, nonhuman primate (NHP) models very accurately model human
PK due to the species similarity in Fc-FcRn binding. However, NHP models carry
significant financial costs as well as significant ethical concerns for testing.
One possible solution to improve clinical relevance while also reducing
dependence on NHP models is to use genetically modified mouse models. In these
models, such as B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr/DcrJ (FcRn Tg32, 014565) and
B6.Cg-Fcgrttm1Dcr Tg(CAG-FCGRT)276Dcr/DcrJ (FcRn Tg276, 004919), the mouse
FcRn is removed in exchange for the human FcRn. This allows for the appropriate
species Fc-FcRn binding affinities that standard mice fail to model.

33 | GENengnews.com


http://www.jax.org/strain/014565 http://www.jax.org/strain/004919 http://www.GENengnews.com

Jax Labs eBook

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