Fibroblast growth factor inducible (Fn14)-specific antibodies concomitantly display signaling pathway-specific agonistic and antagonistic activity

Abstract

Background: Fn14 is a therapeutic target in various diseases. Results: Anti-Fn14 antibodies activate the alternative NFκB pathway but not other Fn14-related activities induced by soluble or membrane-bound TWEAK. FcγR-bound anti-Fn14 antibodies, however, activate the full spectrum of Fn14-associated activities. Conclusion: Anti-Fn14 antibodies elicit agonistic activities differing from those of the natural Fn14 ligand TWEAK. Significance: These findings influence the rationale of designing Fn14-targeted therapies. Copyright © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.