A novel modality of BAFF-specific inhibitor AMG623 peptibody reduces B-cell number and improves outcomes in murine models of autoimmune disease.
OBJECTIVE
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.
Department of Inflammation, Amgen Inc., Thousand Oaks, CA 91320, USA. hhsu@amgen.com
Hailing
H
Hsu
Sanjay D
SD
Khare
Frances
F
Lee
Kent
K
Miner
Yi-Ling
YL
Hu
Marina
M
Stolina
Nessa
N
Hawkins
Qing
Q
Chen
Shu-Yin Joanne
SY
Ho
Hosung
H
Min
Fei
F
Xiong
Tom
T
Boone
Debra J
DJ
Zack
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection
C573858:AMG623 peptibody; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007155:Immunologic Factors; D011993:Recombinant Fusion Proteins; C505719:TNFSF13B protein, human; C505720:Tnfsf13b protein, mouse