Human FcRn transgenic mice for pharmacokinetic evaluation of therapeutic antibodies.
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.
Roopenian
Derry C
DC
The Jackson Laboratory, Bar Harbor, ME, USA.
Christianson
Gregory J
GJ
Sproule
Thomas J
TJ
D000418:Albumins / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D011961:Receptors, Fc / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D019076:Transgenes; D000068878:Trastuzumab
D000418:Albumins; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D000068878:Trastuzumab; C100688:Fc receptor, neonatal