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题名: High throughput cytotoxicity screening of anti-HER2 immunotoxins conjugated with antibody fragments from phage-displayed synthetic antibody libraries.
作者: Shin-Chen Hou;Hong-Sen Chen;Hung-Wei Lin;Wei-Ting Chao;Yao-Sheng Chen;Chi-Yu Fu;Chung-Ming Yu;Kai-Fa Huang;Andrew H.-J. Wang;An-Suei Yang
贡献者: 國立臺灣海洋大學:海洋生物研究所
日期: 2016
上传时间: 2018-05-07T05:52:45Z
出版者: Scientific Reports
摘要: Abstract: Immunotoxins are an important class of antibody-based therapeutics. The potency of the immunotoxins depends on the antibody fragments as the guiding modules targeting designated molecules on cell surfaces. Phage-displayed synthetic antibody scFv libraries provide abundant antibody fragment candidates as targeting modules for the immunoconjugates, but the discovery of optimally functional immunoconjugates is limited by the scFv-payload conjugation procedure. In this work, cytotoxicity screening of non-covalently assembled immunotoxins was developed in high throughput format to discover highly functional synthetic antibody fragments for delivering toxin payloads. The principles governing the efficiency of the antibodies as targeting modules have been elucidated from large volume of cytotoxicity data: (a) epitope and paratope of the antibody-based targeting module are major determinants for the potency of the immunotoxins; (b) immunotoxins with bivalent antibody-based targeting modules are generally superior in cytotoxic potency to those with corresponding monovalent targeting module; and (c) the potency of the immunotoxins is positively correlated with the densities of the cell surface antigen. These findings suggest that screening against the target cells with a large pool of antibodies from synthetic antibody libraries without the limitations of natural antibody responses can lead to optimal potency and minimal off-target toxicity of the immunoconjugates.
關聯: 6
显示于类别:[海洋生物研究所] 期刊論文


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