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展示系统(噬菌体、细菌和酵母展示)在生产抗癌抗体方面的概述;优缺点。

An overview on display systems (phage, bacterial, and yeast display) for production of anticancer antibodies; advantages and disadvantages.

机构信息

Department of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran.

Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran; Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran.

出版信息

Int J Biol Macromol. 2022 May 31;208:421-442. doi: 10.1016/j.ijbiomac.2022.03.113. Epub 2022 Mar 24.

Abstract

Antibodies as ideal therapeutic and diagnostic molecules are among the top-selling drugs providing considerable efficacy in disease treatment, especially in cancer therapy. Limitations of the hybridoma technology as routine antibody generation method in conjunction with numerous developments in molecular biology led to the development of alternative approaches for the streamlined identification of most effective antibodies. In this regard, display selection technologies such as phage display, bacterial display, and yeast display have been widely promoted over the past three decades as ideal alternatives to traditional methods. The display of antibodies on phages is probably the most widespread of these methods, although surface display on bacteria or yeast have been employed successfully, as well. These methods using various sizes of combinatorial antibody libraries and different selection strategies possessing benefits in screening potency, generating, and isolation of high affinity antibodies with low risk of immunogenicity. Knowing the basics of each method assists in the design and retrieval process of antibodies suitable for different diseases, including cancer. In this review, we aim to outline the basics of each library construction and its display method, screening and selection steps. The advantages and disadvantages in comparison to alternative methods, and their applications in antibody engineering will be explained. Finally, we will review approved or non-approved therapeutic antibodies developed by employing these methods, which may serve as therapeutic antibodies in cancer therapy.

摘要

抗体作为理想的治疗和诊断分子,是最畅销的药物之一,在疾病治疗中特别是癌症治疗中具有显著疗效。由于杂交瘤技术作为常规抗体生成方法的局限性,以及分子生物学的众多发展,人们开发了替代方法来简化最有效抗体的识别。在这方面,展示选择技术,如噬菌体展示、细菌展示和酵母展示,作为传统方法的理想替代品,在过去三十年中得到了广泛的推广。在这些方法中,噬菌体上抗体的展示可能是最广泛的方法,尽管细菌或酵母表面展示也已成功应用。这些方法使用各种大小的组合抗体文库和不同的选择策略,在筛选效力、产生和分离低免疫原性的高亲和力抗体方面具有优势。了解每种方法的基础知识有助于设计和检索适合不同疾病(包括癌症)的抗体。在这篇综述中,我们旨在概述每种文库构建及其展示方法、筛选和选择步骤的基础知识。与替代方法相比的优缺点,以及它们在抗体工程中的应用。最后,我们将回顾通过这些方法开发的已批准或未批准的治疗性抗体,它们可能作为癌症治疗中的治疗性抗体。

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