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，具有成本效益的制造过程以商业上生产治疗抗体的需求将继续对生物制药和医疗行业产生巨大的兴趣。与此应用程序相关的长期目标是使用稳定的转基因植物（即拟南芥和生菜）开发新的制造过程，以改善生产过程并证明制造技术的可行性和优势。这些目标是最好通过开发高产的转基因植物来实现模型抗体，并通过与哺乳动物细胞培养中产生的相同抗体相比，通过广泛的表征和测试来证明抗体的功能。用于评估技术和比较目的的模型抗体是一种完全人性化的IgGLK抗组织因子抗体（HOAT），该抗体（HOAT）目前正在作为抗癌治疗前临床前发育。该研究建议的具体目的是：i）开发稳定的转基因拟南芥和生菜的线，产生高产量的HOAT，并产生由稳定的转基因生菜产生的100 mg HOAT抗体； ii）表征植物来源的HOAT，以评估使用体外测试（活性，蛋白质特征），药代动力学和体内抗癌疗效在小鼠异种移植模型中的可比性。所描述的基于植物的系统将是抗体生产的最经济的过程，并且可以以明显较低的商品成本生产这些治疗蛋白，从而使抗体疗法的扩散范围更广泛，尤其是在经济上较低的市场中。将HOAT用作模型蛋白的使用将提供原则证明，证明生产经济学和抗体功能/功效，并导致植物来源的抗体产物，可以将其推进到临床研究中。