YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

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

Tetravalent Bispecific 항체 분자인 Di-diabody의 제조 및 표적 단백질에 대한 항염증 영향

  • 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)
  • 정선기 (충남대학교 약학대학, 형질전환복제돼지센터) ;
  • 류창선 (충남대학교 약학대학, 형질전환복제돼지센터) ;
  • 김선규 (한화케미칼 중앙연구소) ;
  • 마진열 (한국한의학연구원 신한방제제연구센터) ;
  • 김상겸 (충남대학교 약학대학, 형질전환복제돼지센터)
  • Received : 2010.09.10
  • Accepted : 2010.11.22
  • Published : 2010.12.31
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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

References

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