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相关概念视频

Hybridoma Technology01:31

Hybridoma Technology

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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,...
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Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood
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矩阵CDR移植:一种新古典的框架,用于抗体人性化和可开发性.

Pankaj Gupta1, Alexander M Horspool1, Goral Trivedi1

  • 1Biotherapeutics Discovery, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA.

The Journal of biological chemistry
|December 10, 2023
PubMed
概括

人性化抗体涉及平衡目标结合和发展能力. 这项研究表明,优化抗体框架,而不仅仅是序列同质性,可以产生更好的生物治疗候选者,具有更好的特性,用于更快的发展.

关键词:
在CDR中进行CDR接种.生物物理评估评估开发能力 开发能力细菌系的生殖线.人性化的人性化.

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科学领域:

  • 生物技术是生物技术.
  • 免疫学 免疫学 免疫学
  • 蛋白质工程是指蛋白质工程.

背景情况:

  • 开发生物治疗单克隆抗体需要平衡目标参与与物理化学性质.
  • 非人类抗体的人性化对于利用各种抗体发现平台至关重要.
  • 传统的人性化专注于生殖线同质性,经常忽视分子性质.

研究的目的:

  • 评估不同的人类可变区域框架序列对抗体开发能力和功能的影响.
  • 为了评估超越最大序列同质学的互补确定区域框架兼容性.
  • 为了确定人性化的抗体变体,以改善全球性质,用于生物治疗开发.

主要方法:

  • 将小鼠抗LAG3抗体的补充确定区域 (CDR) 移植到不同的人类可变重 (VH) 和可变轻 (VL) 框架库中.
  • 逐步评估移植抗体的表达,亲和力,生物物理开发能力和功能.
  • 使用主要组件分析来评估多种移植框架组合.

主要成果:

  • 特定的VH和VL框架序列显著影响了表达和净化.
  • 较大的VL序列保存与保留或改善的结合亲缘关系相关.
  • VH影响了发育能力,而VL影响了细胞结合和功能;一些非最佳保存的移植物表现出优越的特性.

结论:

  • 现代高通量系统允许对CDR框架组合进行系统分析.
  • 通过优化超出序列同质性的框架选择,可以产生具有改善全球性质的人性化抗体.
  • 这种方法提高了成功开发生物治疗抗体的可能性.