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

Clin Exp Rheumatol. Mar-Apr 2012;30(2):197-201. Epub 2012 Apr 13.

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.

MeSH terms

  • Animals
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • B-Cell Activating Factor / antagonists & inhibitors*
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / metabolism
  • B-Cell Activation Factor Receptor / metabolism
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Cell Proliferation / drug effects
  • Female
  • HEK293 Cells
  • Humans
  • Immunologic Factors / pharmacology*
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Recombinant Fusion Proteins / pharmacology*
  • Time Factors
  • Transfection

Substances

  • AMG623 peptibody
  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Immunologic Factors
  • Recombinant Fusion Proteins
  • TNFSF13B protein, human
  • Tnfsf13b protein, mouse