权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Plant-derived MAb therapeutics for west nile virus

针对西尼罗病毒的植物源性单克隆抗体疗法

基本信息

批准号：
7325989
负责人：
Qiang Chen
金额：
$ 35.72万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7325989
关键词：
Advanced Development American Antibodies Arizona Avidity Binding Biochemical Blood Blood - brain barrier anatomy Capital Cells Central Nervous System Diseases Cessation of life Characteristics Chimeric Proteins Clinical Clinical Trials Communicable Diseases Condition Cost Savings Cyclic GMP Development Diamond Disadvantaged Disease Outbreaks Dose Elderly Emerging Communicable Diseases Encephalitis Ensure Epidemic Epitopes Facility Construction Funding Category Future Generations Globulins Hamsters Human Immune Immunotherapeutic agent In Vitro Infection Infectious Agent Inflammatory Intravenous Immunoglobulins Investments Lateral Left Licensing Meningitis Molecular Biology Monoclonal Antibodies Mus Neuraxis Nicotiana North America Permeability Pharmaceutical Preparations Phase Plantibodies Plants Process Production Proteins Rattus Reagent Recombinants Regulation Research Risk Rodent Safety Supportive care Technology Testing Therapeutic Therapeutic Agents Therapeutic Monoclonal Antibodies Therapeutic antibodies Transferrin Receptor Transgenic Plants Treatment Efficacy Universities Vaccines Variant Vertebrates Virus Diseases Washington West Nile virus bioprocess cost day env Gene Products expression vector improved infected vector rodent medical schools mortality mouse model neoplastic nervous system disorder neutralizing monoclonal antibodies novel novel therapeutics preclinical study prototype scale up vector virus pathogenesis

项目摘要

DESCRIPTION (provided by applicant): The outbreaks of West Nile Virus (WNV) in North America over the last decade indicate its establishment and continued spread throughout the Western hemisphere. At present, no therapeutic or vaccine is available for human use. The continued expanding WNV epidemic demands effective therapeutics and new production technologies that can rapidly transfer them into the clinical setting. The proposed research will advance the development of immunotherapeutics, with an emphasis on technology that allows cost-saving scale-up capability through the use of transgenic plants. The proposed research exploits the facile capability of plant cells to rapidly express and accumulate post-translationally modified proteins, and builds upon our ongoing research to use plant-derived monoclonal antibodies (MAbs) and MAb fusion proteins as therapeutics for viral infections. Recent research has shown that a humanized murine MAb (hu-E16) has promising therapeutic potential. A single dose of hu-E16 protected mice and hamsters against WNV-induced mortality even 5 days after infection. In addition to creating a plant-derived hu-E16 mAb with equivalent activity, this project intends to create a novel blood-brain barrier (BBB) permeable variant to enhance potency and prolong the window of opportunity for treatment. Prototype plant-derived proteins will be produced in quantities sufficient for preclinical trials. We will also develop scale-up and purification technology for subsequent production under cGMP conditions. Transgenic plants are ideal for MAb production since plant-derived MAb and MAb fusion proteins can be rapidly expanded in commercial production without high-capital cost investments for traditional MAb facilities. Thus, in addition to generating novel therapeutic reagents for WNV, this study will provide proof-of-principle for the rapid development and use of "plantibodies" against human infectious diseases. Such technology can then be readily applied in the future to other emerging infectious diseases or bioterrorist threats.

描述（由申请人提供）：西尼罗河病毒（WNV）在过去十年中在北美的爆发表明它在整个西半球的建立和持续传播。目前，没有治疗剂或疫苗可供人类使用。持续扩大的西尼罗河病毒流行需要有效的治疗方法和新的生产技术，可以迅速将它们转移到临床环境中。拟议的研究将推进免疫治疗的发展，重点是通过使用转基因植物实现成本节约的规模化能力。拟议的研究利用植物细胞快速表达和积累翻译后修饰蛋白的能力，并以我们正在进行的研究为基础，使用植物源性单克隆抗体（MAb）和MAb融合蛋白作为病毒感染的治疗方法。最近的研究表明，人源化鼠单克隆抗体（hu-E16）具有很好的治疗潜力。单剂量的hu-E16保护小鼠和仓鼠免于WNV诱导的死亡，甚至在感染后5天。除了创造具有同等活性的植物来源的hu-E16 mAb外，该项目还打算创造一种新的血脑屏障（BBB）可渗透变体，以增强效力并延长治疗的机会窗口。原型植物来源的蛋白质将以足够用于临床前试验的数量生产。我们还将开发放大和纯化技术，用于cGMP条件下的后续生产。转基因植物对于单克隆抗体生产是理想的，因为植物来源的单克隆抗体和单克隆抗体融合蛋白可以在商业生产中快速扩增，而无需对传统单克隆抗体设施进行高资本成本投资。因此，除了产生用于WNV的新型治疗试剂外，本研究还将为快速开发和使用“plantibodies”对抗人类传染病提供原理证明。这种技术今后可以很容易地应用于其他新出现的传染病或生物恐怖主义威胁。