Won-Jae Kwag, Moo-Young Song, Sang-Koo Park, Tae Hyoung Yoo, Seung Hoon Kim, Kyung Mi Park, Hyung Jin Moon, Bongtae Kim, Kyoung Kyu Ahn, Byung-Kyu Lee
언어
영어(ENG)
URL
https://www.earticle.net/Article/A114455
※ 원문제공기관과의 협약기간이 종료되어 열람이 제한될 수 있습니다.
원문정보
초록
영어
TNFα is a important mediator of inflammatory diseases including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), Crohn’s disease, psoriatic arthritis, and ankylosing spondylitis. In recent years, the biologics that inhibit the activity of the TNFα have become a major target for drug developers and it has been recognized that successful treatment strategies for RA. We produced and characterized a murine monoclonal antibody (mAb) TSK114 against human TNFα, and further developed the humanized mAb YHB1411-2 by complementary-determining region (CDR) grafting procedure. The neutralizing activity of YHB1411-2 to inhibit human TNFα-induced cytotoxicity in vitro was tested using WEHI cell based assay system. The neutralizing activity of YHB1411-2 showed 2~3 fold higher than that infliximab and adalimumab. The TNFα neutralizing activity of YHB1411-2 in vivo was evaluated using galactosamine-sensitized mouse model. YHB1411-2 demonstrated a dose-dependent inhibition of mortality and a more potency than infliximab on the same dosage. Epitope mapping was conducted by yeast display technology and site directed mutagenesis. YHB1411-2 has two predominant binding regions located on the apical bottom and top of the subunit surfaces of trimeric TNFα. The therapeutic efficacy of YHB1411-2 was assessed by using transgenic mouse polyarthritis model. In the results, YHB1411-2 dose-dependently prevented the progress of polyarthritis. Especially, the severity of arthritis in Tg mice treated with YHB1411-2 was significantly reduced in comparison with infliximab treated Tg mice at the same dosage in the histopathological evaluation. In summary, our study showed that YHB1411-2 has higher TNFα-inhibitory activity in vitro and in vivo than other TNFα blockers.
한국생물공학회 [The Korean Society for Biotechnology and Bioengineering]
설립연도
1984
분야
공학>생물공학
소개
이 법인은 생물 공학의 발전과 보급에 이바지하고, 회원 상호 간의 연구 협력과 친목을 도모함을 목적으로 한다
1. 생물공학 분야의 발전을 위한 연구 협력
2. 생물공학의 실용화를 촉진시키기 위한 산학 협동
3. 학술연구 발표회, 강연회, 연수회 등 학술활동의 개최
4. 국,영문 학술지,소식지,학술회의 Proceedings 및 학술도서의 발간
5. 생물공학 발전을 위한 정책 건의
6. 기타 국제 교류 등 본 학회의 목적 달성을 위한 제반 활동