The Therapeutic Antibody LM609 Selectively Inhibits Ligand Binding to Human α_Vβ₃ Integrin via Steric Hindrance.

ABSTRACT: The LM609 antibody specifically recognizes α_Vβ₃ integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for α_Vβ₃-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of α_Vβ₃ integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for α_Vβ₃. Using single-particle electron microscopy, we show that LM609 binds at the interface between the β-propeller domain of the α_V chain and the βI domain of the β₃ chain, near th

SUBMITTER: Borst AJ 

PROVIDER: S-EPMC5689087 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature