Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy.

Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy.
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利用噬菌体展示技术制备抗传染病和毒素的重组抗体用于诊断和治疗。

DOI:
10.3389/fcimb.2021.697876
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发表时间:
2021
影响因子:
5.7
通讯作者:
Hust M
Hust M
中科院分区:
医学2区
文献类型:
--
作者:
Roth KDR;Wenzel EV;Ruschig M;Steinke S;Langreder N;Heine PA;Schneider KT;Ballmann R;Fühner V;Kuhn P;Schirrmann T;Frenzel A;Dübel S;Schubert M;Moreira GMSG;Bertoglio F;Russo G;Hust M

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抗体是诊断和治疗由病原体及其毒素引起的疾病所必需的分子。一百多年前,抗体通过使用动物血清来治疗破伤风和白喉,被整合到我们对抗传染病的医学体系中。在这些日子里,大多数开发的治疗性抗体靶向癌症或自身免疫性疾病。2019冠状病毒病大流行提醒我们抗体对于治疗传染病的重要性。虽然自前世纪70年代以来可以通过杂交瘤技术产生单克隆抗体,但如今抗体噬菌体展示以及其他展示技术被稳健地建立以发现新的人单克隆抗体。噬菌体展示是一种体外技术,其赋予了从通用文库产生针对任何可想象的足够大小的分子的抗体的潜力,并且省略了免疫系统的限制。如果恢复期患者或免疫/感染的动物可用,则可以构建免疫噬菌体展示文库以选择体内亲和力成熟的抗体。另一个优点是编码噬菌体展示的抗体片段的DNA序列的可用性,其包装在噬菌体颗粒中。因此,根据最终应用的要求,所选择的抗体片段可以以任何所需的抗体形式快速地进一步工程化。在这篇综述中,我们提出了一个概述噬菌体展示衍生的重组抗体对细菌,病毒和真核病原体,以及微生物毒素,用于诊断和治疗应用。
Antibodies are essential molecules for diagnosis and treatment of diseases caused by pathogens and their toxins. Antibodies were integrated in our medical repertoire against infectious diseases more than hundred years ago by using animal sera to treat tetanus and diphtheria. In these days, most developed therapeutic antibodies target cancer or autoimmune diseases. The COVID-19 pandemic was a reminder about the importance of antibodies for therapy against infectious diseases. While monoclonal antibodies could be generated by hybridoma technology since the 70ies of the former century, nowadays antibody phage display, among other display technologies, is robustly established to discover new human monoclonal antibodies. Phage display is an in vitro technology which confers the potential for generating antibodies from universal libraries against any conceivable molecule of sufficient size and omits the limitations of the immune systems. If convalescent patients or immunized/infected animals are available, it is possible to construct immune phage display libraries to select in vivo affinity-matured antibodies. A further advantage is the availability of the DNA sequence encoding the phage displayed antibody fragment, which is packaged in the phage particles. Therefore, the selected antibody fragments can be rapidly further engineered in any needed antibody format according to the requirements of the final application. In this review, we present an overview of phage display derived recombinant antibodies against bacterial, viral and eukaryotic pathogens, as well as microbial toxins, intended for diagnostic and therapeutic applications.
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