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KMID : 0370220100540060500
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Yakhak Hoeji
2010 Volume.54 No. 6 p.500 ~ p.506
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Production of Di-diabody, a Tetravalent Bispecific Antibody Molecule and its Anti-inflammatory Effects on the Target Proteins
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Jung Sun-Ki
Ryu Chang-Seon
Kim Sun-Kyu
Ma Jin-Yeul
Kim Sang-Kyum
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Abstract
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TNF- 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-. 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-, 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- induced cytotoxicity. Further study to elucidate the pharmacological significance of the Di-diabody is warranted using experimental animals.
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KEYWORD
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rheumatoid arthritis, TNF-alpha, VCAM-1, bispecific antibody, Di-diabody
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