Bone Marrow–Liver–Thymus ( BLT ) Humanized Mice as a Tool to Assess Checkpoint Inhibitor Adverse Events

Humanized mouse models have made significant advances over the past decade and now have the potential to help inform pre-clinical assessment of biological drug products. In this chapter, we discuss our experience using BLT-humanized mice as a tool, to assess their ability to model the adverse events observed in patients treated with checkpoint inhibitors. Among the considerations for using BLT-humanized mice are humanization method, post-surgical humanization monitoring, methods used to quantitate humanization, use of reagents to discern human and murine leukocytes and the impact of mouse strain on results. Another key issue is to evaluate for the potential of pre-existing graft versus host disease that could be confused with adverse events caused by checkpoint inhibitors. Finally, we summarize our findings from studies with checkpoint inhibitors and describe advantages and potential drawbacks of this animal model.