Developments in the production of mucosal antibodies in plants.
Developments in the production of mucosal antibodies in plants.
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DOI：
10.1016/j.biotechadv.2015.11.002
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发表时间：
2016-03
影响因子：
16
通讯作者：
N. Vasilev;C. Smales;S. Schillberg;R. Fischer;A. Schiermeyer
中科院分区：
文献类型：
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作者：
N. Vasilev;C. Smales;S. Schillberg;R. Fischer;A. Schiermeyer
重组粘膜抗体代表了用于开发下一代生物药物的有吸引力的靶分子，所述下一代生物药物用于针对各种感染性疾病的被动免疫和患有粘膜抗体缺陷的患者的治疗。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，因此它们被认为是难以生产的重组蛋白。除了传统的基于拟南芥的生产平台外，植物正在成为这种复杂大分子的替代表达宿主。植物细胞能够产生高质量的粘膜抗体，如在不同植物物种中成功表达的各种抗体形式的分泌性免疫球蛋白A（伊加）和M（IgM）所示，所述不同植物物种包括烟草及其近亲烟草（Nicotiana benthamiana）、玉米、番茄和拟南芥。重要的是，对于生物素应用，转基因植物能够合成功能性伊加和IgM分子，其生物活性和安全性与其天然哺乳动物对应物相当。本文综述了粘膜伊加和IgM抗体的结构和功能，并总结了目前的知识，其生产和加工在植物宿主系统。特别强调考虑细胞内转运过程，因为这些影响成熟免疫球蛋白的组装、其分泌速率、蛋白水解/降解和糖基化模式。此外，这篇评论提供了一个大纲的糖工程的努力，迄今已进行生产抗体与同质的人样聚糖装饰。我们相信，我们对与免疫球蛋白的异源表达相关的植物细胞机制的理解的持续发展将进一步提高来自植物系统的“类人”的翻译后修饰的生产水平、质量和控制，并增强此类分子的监管批准的前景，从而导致植物来源的粘膜抗体的商业开发。
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 relativeNicotiana benthamiana, maize, tomato andArabidopsis 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.