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

• 영문명: Production of Di-diabody, a Tetravalent Bispecific Antibody Molecule and its Anti-inflammatory Effects on the Target Proteins
• 발행기관: 대한약학회
• 저자명: 정선기(Sun Ki Jung) 류창선(Chang Seon Ryu) 김선규(Sun Kyu Kim) 마진열(Jin Yeol Ma) 김상겸(Sang Kyum Kim)
• 간행물 정보: 『약학회지』제54권 제6호 (2010년), 500~506쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2010.12.31

영문 초록

TNF-α 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-α. 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-α, 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-α induced cytotoxicity. Further study to elucidate the pharmacological significance of the Di-diabody is warranted using experimental animals.

키워드

rheumatoid arthritis TNF-alpha VCAM-1 bispecific antibody Di-diabody