Transgenic Plant Technology for Producing Therapeutic Recombinant Antibodies

用于生产治疗性重组抗体的转基因植物技术

• 批准号: 6994054
• 负责人: VALENTIN NEGROUK
• 金额: $ 10万
• 依托单位: ALTOR BIOSCIENCE. LLC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6994054
• 关键词: Arabidopsis; CHO cells; Compositae; antibody; antineoplastics; athymic mouse; biotechnology; biotherapeutic agent; cell line; disease /disorder model; drug design /synthesis /production; drug screening /evaluation; gene expression; genetically modified plants; laboratory mouse; pharmacokinetics; protein structure function; recombinant proteins

DESCRIPTION (provided by applicant): The need to develop novel, cost effective manufacturing processes to produce therapeutic antibodies commercially will continue to be of considerable and growing interest to biopharmaceutical and medical industries. The long-term objectives related to this application are to develop novel manufacturing processes using stable transgenic plants, namely Arabidopsis and lettuce, to improve the production process and demonstrate the feasibility and advantages of the manufacturing technology. These objectives are best accomplished by developing high yielding transgenic plants producing a model antibody and demonstrating the antibody's functionality by extensive characterization and testing in comparison with the same antibody produced in mammalian cell culture. The model antibody used for assessing the technology and comparison purposes is a fully humanized IgGlK anti-tissue factor antibody (hOAT) that is currently in pre-clinical development as an anti-cancer therapeutic. The specific aims of this research proposal are to: i) develop lines of stable transgenic Arabidopsis and lettuce producing high yields of hOAT and produce 100 mg of hOAT antibody produced by stable transgenic lettuce; and ii) characterize the plant-derived hOAT to evaluate comparability to CHO-produced hOAT using in vitro testing (activity, protein characteristics), pharmacokinetics and in vivo anti-cancer efficacy in a mouse xenograft model. The plant-based system described would be one oUhe most economical processes for antibody production and could make it possible to produce these therapeutic proteins at significantly lower cost of goods, enabling wider spread use of antibody therapeutics, particularly in less economically developed markets. The use of hOAT as model protein will provide proof-of-principle, demonstrate production economics and antibody functionality/efficacy and also lead to a plant-derived antibody product that could be advanced into clinical studies.

描述（由申请人提供）： 开发新颖的、具有成本效益的制造工艺来商业化生产治疗性抗体的需求将继续引起生物制药和医疗行业的广泛关注，并且日益增长。与该应用相关的长期目标是利用稳定的转基因植物（即拟南芥和生菜）开发新的制造工艺，以改进生产工艺并展示制造技术的可行性和优势。这些目标最好通过开发产生模型抗体的高产转基因植物并通过与哺乳动物细胞培养物中产生的相同抗体进行广泛的表征和测试来证明抗体的功能来实现。用于评估技术和比较目的的模型抗体是完全人源化的IgG1K抗组织因子抗体(hOAT)，其目前作为抗癌治疗剂处于临床前开发阶段。本研究计划的具体目标是： i) 开发高产 hOAT 的稳定转基因拟南芥和生菜品系，并生产由稳定转基因生菜产生的 100 mg hOAT 抗体； ii) 使用体外测试（活性、蛋白质特征）、药代动力学和小鼠异种移植模型中的体内抗癌功效来表征植物源性 hOAT，以评估与 CHO 生产的 hOAT 的可比性。所描述的基于植物的系统将是最经济的抗体生产工艺之一，并且可以以显着较低的产品成本生产这些治疗性蛋白质，从而使抗体疗法能够更广泛地使用，特别是在经济欠发达的市场。使用 hOAT 作为模型蛋白将提供原理验证，展示生产经济性和抗体功能/功效，并产生可进入临床研究的植物源抗体产品。