Basic study for establishment of novel antibody therapy for hemophilia A with an antibody enhancing factor VIII activity

建立新型抗体增强因子VIII活性的A型血友病抗体疗法的基础研究

• 批准号: 20591259
• 负责人: SHIMA Midori
• 金额: $ 3.24万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591259/
• 关键词: 小児血液学; 第VIII因子; 第VIII因子活性; 血友病A; 活性化; モノクローナル抗体; トロンビン; 活性型第X因子; A2ドメイン; 抗体療法

Antibodies that promote FVIII activity do not appear to have been reported. In this study, anti-FVIII monoclonal antibody, mab216, that enhanced FVIII coagulation activity. The mab216 increased FVIII activity ～1.5-fold dose-dependently, FXa generation and thrombin generation were increased by ～1.4- and ～2.5-fold, respectively. An anti A2 epitope was identified and the antibody enhanced the cleavage at Arg372. The findings may cast new light on new principles for improving the treatment of haemophilia A patients.

促进FVIII活性的抗体似乎还没有报道。在本研究中，抗FVIII的单抗mab216可增强FVIII的凝血活性。单抗216可使FVIII活性增加1.5倍，FXA和凝血酶生成分别增加1.4倍和2.5倍。确定了一个抗A2表位，该抗体促进了Arg372的切割。这一发现可能为改进血友病A患者治疗的新原则提供新的曙光。

项目成果

Characterisation of an antibody specific for coagulation factor VIII that enhances factor VIII activity.

增强凝血因子 VIII 活性的凝血因子 VIII 特异性抗体的表征。

• 发表时间: 2010
• 期刊: Thromb Haemost 103(1)
• 作者: Takeyama M;Nogami K;Matsumoto T;Soeda T;Suzuki T;Hattori K;Shima M.
• 通讯作者: Shima M.

The factor villa C2 domain (residues 2228-2240) interacts with the factor Ixa Gla domain in the factor xase complex.

因子villa C2 结构域（残基2228-2240）与因子xase 复合物中的因子Ixa Gla 结构域相互作用。

• 发表时间: 2009
• 期刊: Journal of Biological Chemistry 284
• 作者: Soeda T;Nogami K;Nishiya K;Takeyama M;Ogiwara K;Sakata Y;Yoshioka A;Shima M.
• 通讯作者: Shima M.

Anti-A2 monoclonal antibody enhancing thrombin(and factor Xa)-catalyzed factor VIII activity

抗 A2 单克隆抗体增强凝血酶（和因子 Xa）催化的因子 VIII 活性

• 发表时间: 2009
• 作者: Takeyama M;Nogami K;Soeda T;Ogiwara K;Nishiya K;Shima M.
• 通讯作者: Shima M.

Engineering Liver Tissues Under the Kidney Capsule Site Provides Therapeutic Effects to Hemophilia B Mice

• DOI: 10.3727/096368910x508924
• 发表时间: 2010-01-01
• 期刊: CELL TRANSPLANTATION
• 影响因子: 3.3
• 作者: Ohashi, Kazuo;Tatsumi, Kohei;Okano, Teruo
• 通讯作者: Okano, Teruo

Determination of a factor VIII-interactive region within plasmin responsible for plasmin-catalysed activation and inactivation of factor VIII(a)

确定纤溶酶内负责纤溶酶催化激活和失活因子 VIII(a) 的因子 VIII 相互作用区域

• 发表时间: 2010
• 期刊: Thromb Haemost,Epub 5;104(1)
• 作者: Nishiya K;Nogami K;Okada K;Matsuo O;Takeyama M;Ogiwara K;Shima M.
• 通讯作者: Shima M.