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. The Fn14-specific monoclonal antibodies PDL192 and P4A8, which are under consideration in clinical trials, showed no agonistic activity with respect to IL8 production and cell death induction. However, oligomerization with protein G or binding to Fcγ recep

SUBMITTER: Salzmann S 

PROVIDER: S-EPMC3650383 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature