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首页> 外文期刊>Biotechnology Advances: An International Review Journal >Developments in the production of mucosal antibodies in plants
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Developments in the production of mucosal antibodies in plants

机译：植物粘膜抗体生产的发展

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Recombinant mucosal antibodies represent attractive target molecules for the development of next generation biopharmaceuticals for passive immunization against various infectious diseases and treatment of patients suffering from mucosal antibody deficiencies. As these polymeric antibodies require complex post-translational modifications and correct subunit assembly, they are considered as difficult-to-produce recombinant proteins. Beside the traditional, mammalian-based production platforms, plants are emerging as alternative expression hosts for this type of complex macromolecule. Plant cells are able to produce high-quality mucosal antibodies as shown by the successful expression of the secretory immunoglobulins A (IgA) and M (IgM) in various antibody formats in different plant species including tobacco and its close relative Nicotiana benthamiana, maize, tomato and Arabidopsis thaliana. Importantly for biotherapeutic application, transgenic plants are capable of synthesizing functional IgA and IgM molecules with biological activity and safety profiles comparable with their native mammalian counterparts. This article reviews the structure and function of mucosal IgA and IgM antibodies and summarizes the current knowledge of their production and processing in plant host systems. Specific emphasis is given to consideration of intracellular transport processes as these affect assembly of the mature immunoglobulins, their secretion rates, proteolysis/degradation and glycosylation patterns. Furthermore, this review provides an outline of glycoengineering efforts that have been undertaken so far to produce antibodies with homogenous human-like glycan decoration. We believe that the continued development of our understanding of the plant cellular machinery related to the heterologous expression of immunoglobulins will further improve the production levels, quality and control of post-translational modifications that are 'human-like' from plant systems and enhance the prospects for the regulatory approval of such molecules leading to the commercial exploitation of plant-derived mucosal antibodies. (C) 2015 Elsevier Inc. All rights reserved.
机译：重组粘膜抗体代表了有吸引力的靶分子，用于开发下一代生物药物，可针对各种传染性疾病进行被动免疫以及治疗粘膜抗体缺乏症的患者。由于这些聚合抗体需要复杂的翻译后修饰和正确的亚基组装，因此被认为是难以生产的重组蛋白。除了基于哺乳动物的传统生产平台外，植物正在作为这类复杂大分子的替代表达宿主而出现。植物细胞能够产生高质量的粘膜抗体，如分泌性免疫球蛋白A（IgA）和M（IgM）在不同植物物种（包括烟草及其近亲烟草），玉米，番茄中以各种抗体形式成功表达所显示的那样。和拟南芥。对于生物治疗应用而言，重要的是，转基因植物能够合成功能性IgA和IgM分子，其生物学活性和安全性与其天然哺乳动物相当。本文回顾了粘膜IgA和IgM抗体的结构和功能，并总结了它们在植物宿主系统中生产和加工的最新知识。特别强调考虑细胞内转运过程，因为它们会影响成熟的免疫球蛋白的组装，它们的分泌速率，蛋白水解/降解和糖基化模式。此外，本综述提供了糖工程的概述，迄今为止已经进行了糖工程的努力，以产生具有均质的人样聚糖修饰的抗体。我们相信，对与免疫球蛋白异源表达有关的植物细胞机制的理解的不断发展，将进一步提高植物系统“类人”的生产水平，质量和翻译后修饰的控制，并提高前景此类分子的监管批准，导致了植物来源的粘膜抗体的商业开发。 （C）2015 Elsevier Inc.保留所有权利。

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