Sheshukova E V, Komarova T V, Dorokhov Y L
Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 119991, Russia.
Biochemistry (Mosc). 2016 Oct;81(10):1118-1135. doi: 10.1134/S0006297916100102.
Like animal cells, plant cells bear mechanisms for protein synthesis and posttranslational modification (glycosylation and phosphorylation) that allow them to be seriously considered as factories for therapeutic proteins, including antibodies, with the development of biotechnology. The plant platform for monoclonal antibody production is an attractive approach due to its flexibility, speed, scalability, low cost of production, and lack of contamination risk from animal-derived pathogens. Contemporary production approaches for therapeutic proteins rely on transgenic plants that are obtained via the stable transformation of plant cells as well as the transient (temporary) expression of foreign proteins. In this review, we discuss present-day approaches for monoclonal antibody production in plants (MAPP), features of carbohydrate composition, and methods for the humanization of the MAPP carbohydrate profile. MAPPs that have successfully passed preclinical studies and may be promising for use in clinical practice are presented here. Perspectives on using MAPPs are determined by analyzing their economic benefits and production rates, which are especially important in personalized cancer therapy as well as in cases of bioterrorism and pandemics.
与动物细胞一样,植物细胞具备蛋白质合成和翻译后修饰(糖基化和磷酸化)机制,随着生物技术的发展,这使得植物细胞有理由被视为生产治疗性蛋白质(包括抗体)的工厂。由于其灵活性、速度、可扩展性、低成本生产以及不存在动物源性病原体污染风险,利用植物生产单克隆抗体的平台是一种颇具吸引力的方法。当代治疗性蛋白质的生产方法依赖于通过植物细胞稳定转化获得的转基因植物以及外源蛋白质的瞬时(临时)表达。在这篇综述中,我们讨论了目前植物中单克隆抗体生产的方法(MAPP)、碳水化合物组成特点以及使MAPP碳水化合物谱人源化的方法。本文还介绍了已成功通过临床前研究且有望用于临床实践的MAPP。通过分析其经济效益和生产率来确定使用MAPP的前景,这在个性化癌症治疗以及生物恐怖主义和大流行情况下尤为重要。