A novel modality of BAFF-specific inhibitor AMG623 peptibody reduces B-cell number and improves outcomes in murine models of autoimmune disease.

Abstract:

OBJECTIVES:AMG623, also known as A-623, is an antagonist of B-cell activating factor (BAFF). The present study was to evaluate the effects of AMG623 on murine models of autoimmune diseases. METHODS:AMG623 was generated through phage library. Inhibitory activities of AMG623 against human and murine BAFF were measured by biacore binding and BAFF-mediated B-cell proliferation assay. Pharmacological effects of AMG623 were studied in BALB/c mice, collagen-induced arthritis model (CIA) and in the NZBxNZW F1 lupus model. RESULTS:AMG623 binds to both soluble and cell surface BAFF. AMG623 blocks both human murine BAFF binding to the receptors. Treatment of AMG623 resulted in B-cell number reduction, and improvement of arthritis and lupus development in mice. CONCLUSIONS:AMG623 is a novel modality of BAFF antagonist. AMG623 is a potential therapeutic agent for the treatment of SLE, rheumatoid arthritis, and other B-cell-mediated autoimmune diseases.

journal_name

Clin Exp Rheumatol

authors

Hsu H,Khare SD,Lee F,Miner K,Hu YL,Stolina M,Hawkins N,Chen Q,Ho SY,Min H,Xiong F,Boone T,Zack DJ

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

197-201

issue

2

eissn

0392-856X

issn

1593-098X

pii

4880

journal_volume

30

pub_type

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