使用遗传编码的非自然氨基酸合成双特异性抗体
Chan Hyuk Kim1, Jun Y Axup, Anna Dubrovska
1Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|May 31, 2012
概括
研究人员使用非自然氨基酸设计了双特异性抗体,以精确向癌症. 这种新的方法产生了强大的抗HER2/抗CD3抗体,在临床前的细胞向和细胞毒性研究中显示出高效.
科学领域:
- 生物技术和免疫学 生物技术和免疫学
- 抗体工程 抗体工程
- 分子生物学分子生物学
背景情况:
- 双特异性抗体通过同时接触多个点,提供有针对性的治疗潜力.
- 目前用于双特异抗体构造的方法可能是复杂的,并产生异质的产品.
- 基因编码的非自然氨基酸为新型蛋白质工程提供了一个多功能平台.
研究的目的:
- 开发一种新的方法,使用遗传编码的非自然氨基酸构建同质双特异性抗体.
- 合成和表征一种抗HER2/抗CD3双特异性抗体.
- 评估合成的双特异抗体在细胞交叉链接和细胞毒性的体外疗效.
主要方法:
- 利用基因编码的非自然氨基酸与正交的化学反应性用于抗体的构建.
- 采用两步合成过程,以确保产品的一致性和高产量.
- 构建了针对HER2表达瘤细胞和CD3表达免疫细胞的抗HER2/抗CD3双特异性抗体.
主要成果:
- 通过精简的两步过程,通过优异的产量获得同质的双特异性抗体产品.
- 通过合成的双特异性抗体证明了HER2阳性细胞和CD3阳性细胞的有效交叉链接.
- 在皮科莫尔度下观察到强烈的实验室效应细胞介导的细胞毒性,表明高生物活性.
结论:
- 使用非天然氨基酸的新方法使同质双特异抗体能够高效精确地构建.
- 合成的抗HER2/抗CD3双特异抗体显示了针对癌症免疫治疗的显著潜力.
- 这种方法为开发下一代双特异抗体疗法提供了一个有希望的策略,具有增强的效能和特异性.
更多相关视频
13:53Homogeneous Glycoconjugate Produced by Combined Unnatural Amino Acid Incorporation and Click-Chemistry for Vaccine Purposes
Published on: December 19, 2020
10:24Genetic Incorporation of Biosynthesized L-dihydroxyphenylalanine (DOPA) and Its Application to Protein Conjugation
Published on: August 24, 2018
相关概念视频
Hybridoma Technology
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, polyethylene glycol...
Hybridoma Selection
Commonly used fusion techniques — electroporation, polyethylene glycol...
Synthetic Biology
Synthetic biology is an interdisciplinary science that involves using principles from disciplines such as engineering, molecular biology, cell biology, and systems biology. It involves remodeling existing organisms from nature or constructing completely new synthetic organisms for applications such as protein or enzyme production, bioremediation, value-added macromolecule production, and the addition of desirable traits to crops, to name a few.
Golden rice
Golden rice is a genetically modified...
Golden rice
Golden rice is a genetically modified...
Tagging and Fusion Proteins
Proteins are involved in several cellular processes and biochemical reactions. Analyzing a specific protein of interest requires it to be isolated from the other proteins in the cell. This is achieved by overexpressing the specific gene in a suitable host to produce large quantities of the target protein. A tag or label is recombined with the gene to produce a fusion protein containing the target protein and the tag. The tags on these fusion proteins can then be used for easy detection and...
Antibody Structure
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...
Production of Pharmaceuticals
Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...
