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Production of Di-diabody, a Tetravalent Bispecific Antibody Molecule and its Anti-inflammatory Effects on the Target Proteins  

Jung, Sun-Ki (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University)
Ryu, Chang-Seon (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University)
Kim, Sun-Kyu (Hanwha Chemical R&D Center)
Ma, Jin-Yeol (Center for Herbal Medicine Improvement Research, Korea Institute of Oriental Medicine)
Kim, Sang-Kyum (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University)
Publication Information
YAKHAK HOEJI / v.54, no.6, 2010 , pp. 500-506 More about this Journal
Abstract
TNF-${\alpha}$ and VCAM-1 play a pivotal role in the pathogenesis of rheumatoid arthritis, and the development of drugs targeting these molecules has extended the therapeutical approaches to rheumatoid arthritis patients. Bispecific antibodies combine the antigen-binding sites of two antibodies within a single molecule and thus they are able to bind to two different epitopes simultaneously. A specific bispecific antibody format termed "Di-diabody" was made for the efficient approach to anti-inflammation. In this study, the DNA vector construct of Di-diabody was built up against two antigens, VCAM-1 and TNF-${\alpha}$. For evaluating this Di-diabody as a bispecific antibody on the efficacy of anti-inflammation, the proteins were analyzed according to each antigen binding affinity and cell based assay related separate molecules. The 7H/Humira Di-diabody produced in this study interacted with its ligands, VCAM-1 and TNF-${\alpha}$, respectively. Also, this antibody exhibited the similar functional activities as compared to 7H-IgG in respect to inhibition of hVCAM-1-induced cell adhesion and Humira-IgG in respect to inhibition of TNF-${\alpha}$ induced cytotoxicity. Further study to elucidate the pharmacological significance of the Di-diabody is warranted using experimental animals.
Keywords
rheumatoid arthritis; TNF-alpha; VCAM-1; bispecific antibody; Di-diabody;
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