Preclinical characterization of Pan-NKG2D ligand-binding NKG2D receptor decoys

NKG2D and its ligands are critical regulators of protective immune responses controlling infections and cancer, defining a crucial immune signaling axis. Current therapeutic efforts targeting this axis almost exclusively aim at enhancing NKG2D-mediated effector functions. However, this axis can drive disease processes when dysregulated, in particular, driving stem -like cancer cell reprogramming and tumorigenesis through receptor/ligand self -stimulation on tumor cells. Despite complexities with its structure and biology, we developed multiple novel engineered proteins that functionally serve as axis -blocking NKG2D "decoys " and report biochemical, structural, in vitro , and in vivo evaluation of their functionality.