Humanized PD-1, B7-H1 (PD-L1) and combination PD-1/B7-H1 (PD-L1) Knock-In Mouse Models
Mayo Clinic researchers have produced humanized PD-1 and B7-H1 (PD-L1) mice using a homozygous “knock-in” strategy to meet the need for an in vivo model that can be used in the development of safe and effective drugs targeting PD-1 and B7-H1. The exons encoding the ligand binding extracellular Ig like domains of the endogenous murine PD-1 or B7-H1 gene, or both, have been replaced with the equivalent exons from the human PD-1 or B7-H1 gene. The resulting mice express human B7-H1, PD-1, or both, on the surface of cells while keeping the murine intracellular domain intact to preserve endogenous function (i.e. signal transduction). These humanized mice, which express human/mouse chimeric PD-1, B7-H1, or both, are produced on a C57BL/6 background, a syngeneic background utilized in the establishment of many tumor models. These in vitro models can be utilized in the study a candidate drug’s ability to block the binding of B7-H1 and PD-1, while allowing for the study of the in vivo distribution and the potential impact that a candidate drug has on the function of normal immune cells.