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.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roland 10.13039/100014345Strong reports financial support was provided by 10.13039/100000060National Institute of Allergy and Infectious Diseases. Roland 10.13039/100014345Strong reports financial support was provided by 10.13039/100000002National Institutes of Health. Roland 10.13039/100014345Strong reports financial support was provided by 10.13039/100000054National Cancer Institute. Roland 10.13039/100014345Strong reports financial support was provided by US 10.13039/100000015Department of Energy. Roland 10.13039/100014345Strong reports financial support was provided by 10.13039/100001906Washington Research Foundation. Roland Strong has patent NKG2D DECOYS issued to Fred Hutchinson Cancer Center. Veronika Groh has patent NKG2D DECOYS issued to Fred Hutchinson Cancer Center. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2024 The Authors. Published by Elsevier Ltd.)