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A novel modality of BAFF-specific inhibitor AMG623 peptibody reduces B-cell number and improves outcomes in murine models of autoimmune disease
H. Hsu, S.D. Khare, F. Lee, K. Miner, Y.-L. Hu, M. Stolina, N. Hawkins, Q. Chen, S.-Y. Ho, H. Min, F. Xiong, T. Boone, D.J. Zack
CER4624
2012 Vol.30, N°2
PI 0197, PF 0201
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PMID: 22325420 [PubMed]
Received: 29/03/2011
Accepted : 20/09/2011
In Press: 13/04/2012
Published: 13/04/2012
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.
