Humanizing Animal Models: A Key to Autoimmune Diabetes Treatment

Preclinical evaluation of antibody-based immunotherapies for the treatment of type 1 diabetes (T1D) in animal models is often hampered by the fact that the human antibody drug does not cross-react with its mouse counterpart. In this issue of Science Translational Medicine, researchers describe a new mouse model that expresses the human isoform of a molecule targeted by T1D antibody therapies that are currently being tested in clinical trials-the human epsilon chain of the CD3 complex expressed on T cells. Anti-CD3 is capable of reducing insulin needs in individuals with recently diagnosed T1D; however, the precise underlying mechanisms of action and the minimal effective dose have been difficult to define. The new humanized mouse model will be instrumental in optimizing anti-CD3-based therapies and accelerating their clinical realization.