Chapter 11 - Humanized Mice in Translational Immunology

Abstract

Many of the next generation therapeutics are based on human cells or human-specific antibodies. Surrogate immunocompetent mouse models are employed using similar mouse-specific cell and antibody reagents to understand potential efficacy and underlying mechanisms, but this does not test directly the safety, efficacy, or mechanism of action of the human-specific reagents poised to enter clinical trials. To address this, humanized mice (ie, immunodeficient mice engrafted with functional human cells and tissues) have been employed as a preclinical bridge between mouse studies and clinical trials. Significant advances have been achieved in the development of mice engrafted with functional human immune systems since the description of immunodeficient mice expressing a mutation in the IL2-receptor common gamma chain in the early 2000s. In this chapter, we describe these advances and the utility of humanized mice for translating the next generation of cell-based and immunomodulatory therapies into the clinic.