IMPROVEMENT OF THE COTTON RAT MODEL OF HUMAN DISEASES

人类疾病棉鼠模型的改进

• 批准号: 6343926
• 负责人: GREGORY A. PRINCE
• 金额: $ 71.78万
• 依托单位: VIRION SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-10 至 2002-12-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6343926
• 关键词: B lymphocyte; CD4 molecule; CD8 molecule; T lymphocyte; antibody formation; cytokine; disease /disorder model; immunogenetics; laboratory rat; molecular cloning; monoclonal antibody; polymerase chain reaction; sectioning; surface antigens; tissue /cell culture

In 1995 the Food and Drug Administration licensed RespiGam TM, a plasma- derived polyclonal IgG formulation, for the prevention of severe respiratory syncytial virus (RSV) pneumonia. In December, 1997, a Biologic License Application was submitted to the FDA for a second- generation RSV preventive, Synagis TM, the first monoclonal antibody ever shown in clinical trials to have efficacy against an infectious agent. These two events underscore the importance of the inbred cotton rat (Sigmodon species) in biomedical research, since all of the preclinical data supporting both drugs were generated in the cotton rat model of RSV infection. However, there are other pressing biomedical issues, involving candidate RSV vaccine safety; HIV, influenza, herpes simplex, measles and parainfluenza viruses; exotic and emerging viruses; and genetic and cancer therapy using adenovirus vectors, for all of which the cotton rat appears to be a preferred model. These issues cannot be addressed adequately because the complexity of the underlying biology requires immunologic and genetic reagents specific for the cotton rat, which are not yet available. We have already begun a program, using methodologies of immunology and molecular biology, to generate the reagents which will allow state-of-the-art studies in this model. The proposed workscope of this application is to develop a library of reagents directed against cotton rat cell-surface antigens, cytokines and chemokines.

1995年，美国食品药品监督管理局（1995 衍生的多克隆IgG公式，以预防严重 呼吸综合病毒（RSV）肺炎。 1997年12月， 生物许可申请已提交给FDA，第二次 RSV一代预防性，下沿TM，第一种单克隆抗体 在临床试验中显示出具有感染力的功效 代理人。 这两个事件强调了近交棉的重要性 生物医学研究中的大鼠（Sigmodon物种），因为所有 棉花大鼠中都产生了支持两种药物的临床前数据 RSV感染的模型。 但是，还有其他紧迫的生物医学 问题，涉及候选RSV疫苗安全；艾滋病毒，流感，疱疹 单纯形，麻疹和副粉虫病毒；异国情调和新兴病毒； 以及使用腺病毒载体的遗传和癌症治疗 棉花大鼠似乎是首选模型。 这些问题 由于基础的复杂性，无法充分解决 生物学需要特有的免疫和遗传试剂 棉鼠，尚不可用。 我们已经开始 程序，使用免疫学和分子生物学方法论 生成将允许最新研究的试剂 模型。 此应用程序的拟议工作台是开发 针对棉大鼠细胞表面抗原的试剂库， 细胞因子和趋化因子。