针对补充成分5的双特异性VHH抗体furulimab (ALXN1720) 的表征,并设计用于小量的皮下注射
Siddharth Jindal1, Dennis Vestergaard Pedersen2, Nimish Gera1
1Alexion, AstraZeneca Rare Disease, 100 College Street, New Haven, CT 06510, USA.
Molecular immunology
|December 24, 2023
概括
格弗鲁利马布是一种新型双特异性抗体,旨在用于皮下治疗补充介导疾病. 它有效地抑制补充成分5 (C5) 激活,显示出治疗相关慢性疾病的希望.
科学领域:
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
背景情况:
- 慢性疾病可能涉及终端补体通路.
- 目前的治疗方法可能缺乏皮下治疗的选择.
- 向补充成分5 (C5) 是一种治疗策略.
研究的目的:
- 开发fegurulimab,一种用于皮下注射的双特异抗体.
- 评估fefurulimab在抑制终端补充通路中的有效性.
- 为了描述fefurulimab的结合和抑制性质.
主要方法:
- 从拉玛图书馆中分离和人性化针对C5和HSA的VHH抗体.
- 使用解离速率常数对furulimab与C5和HSA的结合动力学的表征.
- 在Wieslab测定中评估fefurulimab对终端补充活性的抑制.
- 使用电子显微镜和X射线晶体学进行结构分析.
主要成果:
- 格弗鲁利马布证明了人类终端补充活性的强烈抑制.
- 观察到与人类C5 (54 pM) 和HSA (0.9 nM) 的高亲缘关系结合.
- 该抗体与Cynomolgus子C5和白蛋白进行交叉反应.
- 结构研究表明,C5结合的VHH针对特定的域,防止转化酶结合.
- 格弗鲁利马布抑制了由罕见的C5基变异体介导的补充活性.
结论:
- 格弗鲁利马布是一种具有良好的特征双特异性抗体,具有潜在的皮下输送.
- 它有效地抑制补充成分5 (C5) 裂变和下游激活.
- 格弗鲁利马布显示为补充介导疾病的治疗候选人有前途.
关键词:
ALXN172020 ALXN17202020 ALXN172020 ALXN172020 ALXN172020 ALXN1720双特定的VHH抗体对抗体.补充成分C5和专蛋白.补充介导疾病 补充介导疾病格弗鲁利马布的使用方法更多相关视频
07:25In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
Published on: May 4, 2017
17.8K
04:47A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
7.8K
相关概念视频
01:26Antibody Actions
1.1K
Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
1.1K
01:10Antibody Structure
60.2K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
60.2K
01:31Hybridoma Technology
14.8K
Hybridoma technology is used for the large-scale production of monoclonal antibodies. Monoclonal antibodies bind to only a single antigenic determinant or epitope. Such antibodies are used in research, diagnostics, and disease therapy. The hybridoma technology established in 1975 by Georges Köhler and Cesar Milstein was awarded the Nobel Prize in Medicine in 1984 for revolutionizing research and therapy.
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
14.8K