Transgenic mice, pharmacokinetic

Key words Monoclonal antibodies, Fc-fusion proteins, FcRn, transgenic mice, pharmacokinetics, serum half-life. 

Therapeutic monoclonal antibodies are widely recognized to be a most promising means to treat an increasing number of human diseases, including cancers and autoimmunity. To a large extent, the efficacy of monoclonal antibody treatment is because IgG antibodies have greatly extended persistence in vivo. However, conventional rodent models do not mirror human antibody pharmacokinetics. The key molecule responsible for the extended persistence antibodies is the major histocompatibility complex class I family Fc receptor, FcRn. We describe human FcRn transgenic mouse models and how they can be exploited productively for the preclinical pharmacokinetic evaluation of therapeutic antibodies. 

Figure 7 Pharmacokinetic properties and in vivo gene expression of stabilized plasmid-lipid particles (SPLP). (A) The levels of intact plasmid DNA (pDNA) in the circulation resulting from IV injection of naked plamid pDNA ( ), lipoplexes (O), and SPLP ( ) were determined by Southern blot analysis of plasma samples (100 pg pDNA/mouse). (B) Transgene expression at a distal tumor site resulting from rv injection of naked plamid pDNA ( ), plamid pDNA-cationic liposome complexes (O), and SPLP ( ).

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