SBIR RAPID: Plant Bioproduction of Antibodies for the Treatment of Ebola Infection

SBIR RAPID：用于治疗埃博拉感染的植物生物生产抗体

• 批准号: 1510898
• 负责人: Ryan Shepherd
• 金额: $ 20万
• 依托单位: PhylloTech Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-15 至 2016-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1510898&HistoricalAwards=false
• 关键词: SBIR; RAPID; Plant; Bioproduction; Antibodies

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Rapid Response Research (RAPID) project will be the development of genetically engineered tobacco plants that produce antibodies for the treatment of individuals infected with the Ebola virus. In the current Ebola outbreak, a new drug was tested in infected patients that is based on a tobacco-produced Ebola antibody cocktail called ZMapp (Mapp Biopharmaceutical, Inc, San Diego, CA). Unfortunately, the company's supply of antibody was quickly depleted, and the manufacturing method was not able to keep up with demand. The technological innovation in this proposal is the targeted production of antibodies within the gland cells of the tobacco leaf surface structures called glandular secreting trichomes. The research objectives will be to demonstrate the secretion of antibodies to the Ebola virus from trichome glands. The goal is to generate a line of N. tabacum plants that is optimized for antibody production in plant trichomes to provide an urgently needed biomanufacturing platform for the large-scale production of antibodies that may be used in the treatment of Ebola infection.This SBIR RAPID project proposes to use a recently developed plant-based biomanufacturing system to scale-up the production of antibodies to the Ebola virus for use as a therapeutic. Mapp Biopharmaceutical has produced a drug based on antibodies to the Ebola virus produced in a tobacco plant transient gene expression system. Using this system, they have identified a glycosylated antibody variant (glycoform) with enhanced antibody-dependent cell cytotoxicity. Using glycosyl-transferase knockout lines of N. benthiamiana and transient expression strategies, the company utilizes plants to produce glycosylated antibodies that produce optimal recruitment of natural immune effector cells. Other expression hosts (Chinese hamster ovary cells, yeast) yield product with reduced potency, and are not considered suitable alternatives. To recover active antibody with their current plant expression technology, Mapp Biopharmaceutical must destructively harvest plants, and isolate antibody from plant tissue homogenates. Unfortunately, this method has not been able to produce enough antibodies to satisfy the demand. The proposed method will allow for the production of antibodies in tobacco plants in large scale. In addition, the proposed system will use antibody harvesting strategies that do not require destructive homogenization as the antibodies will be secreted onto the surface of the leaf, and recovered by washing. The goals of this project are to demonstrate secretion of Ebola antibodies, and to generate a line of N. tobacum for optimized antibody glycosylation.

这个小企业创新研究（SBIR）快速反应研究（RAPID）项目的更广泛的影响/商业潜力将是开发基因工程烟草植物，生产用于治疗埃博拉病毒感染者的抗体。在目前的埃博拉疫情中，一种新的药物在感染患者中进行了测试，该药物基于烟草产生的埃博拉抗体鸡尾酒，称为ZMapp（Mapp Biopharmacology，Inc，San Diego，CA）。不幸的是，该公司的抗体供应很快耗尽，制造方法无法跟上需求。该提案中的技术创新是在烟叶表面结构的腺细胞内有针对性地产生抗体，该结构称为腺分泌毛状体。研究目标将是证明毛状腺分泌埃博拉病毒抗体。我们的目标是生成一条N的直线。该SBIR RAPID项目建议使用最近开发的基于植物的生物制造系统来扩大埃博拉病毒抗体的生产规模，以用作治疗药物。Mapp生物制药公司生产了一种基于烟草植物瞬时基因表达系统中产生的埃博拉病毒抗体的药物。 使用该系统，他们已经鉴定出具有增强的抗体依赖性细胞毒性的糖基化抗体变体（糖型）。利用N. benthiamiana和瞬时表达策略，该公司利用植物生产糖基化抗体，产生天然免疫效应细胞的最佳招募。其他表达宿主（中国仓鼠卵巢细胞、酵母）产生的产物效价降低，因此不被视为合适的替代品。为了利用现有的植物表达技术回收活性抗体，Mapp Biopharmaceutical必须破坏性地收获植物，并从植物组织匀浆中分离抗体。不幸的是，这种方法无法产生足够的抗体来满足需求。 所提出的方法将允许在烟草植物中大规模生产抗体。 此外，所提出的系统将使用不需要破坏性均质化的抗体收获策略，因为抗体将分泌到叶子的表面上，并通过洗涤回收。该项目的目标是证明埃博拉病毒抗体的分泌，并产生一个N。优化抗体糖基化。