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Title 

A dual target-directed agent against interleukin-6 receptor and tumor necrosis factor α ameliorates experimental arthritis

Authors 

Y KimH YiH JungY A LimN ParkJ KimS M JungS H ParkYoung Woo ParkJ H Ju

Publisher 

Nature Publishing Group

Issue Date 

2016

Citation 

Scientific Reports, vol. 6, no. 0, pp. 20150-20150

Abstract 

A considerable proportion of patients with rheumatoid arthritis (RA) do not respond to monospecific agents. The purpose of our study was to generate a hybrid form of biologics, targeting tumor-necrosis factor alpha (TNFα) and interleukin-6 receptor (IL-6R), and determine its anti-arthritic properties in vitro and in vivo. A novel dual target-directed agent (DTA(A7/sTNFR2)) was generated by conjugating soluble TNF receptor 2 (sTNFR2) to the Fc region of A7, a new anti-IL-6R antibody obtained by screening the phage display human antibody library. DTA(A7/sTNFR2) inhibited the proliferation and migration of fibroblast-like synoviocytes from patients with RA (RA-FLS) more efficiently than single target-directed agents. DTA(A7/sTNFR2) also blocked osteoclastogenesis from bone marrow cells. The arthritis severity scores of the experimental arthritis mice with DTA(A7/sTNFR2) tended to be lower than those of mice with IgG, A7, or sTNFR2. Histological data suggested that DTA(A7/sTNFR2) is more efficient than single-target drugs in preventing joint destruction and bone loss. These results were confirmed in vivo using the minicircle system. Taken together, the results show that DTA(A7/sTNFR2) may be a promising therapeutic agent for the treatment of RA.

ISSN 

2045-2322

Link 

http://dx.doi.org/10.1038/srep20150

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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