ANTI-HPV HUMAN MONOCLONALS FOR A VAGINAL MICROBICIDE

用于阴道杀菌剂的抗 HPV 人单克隆抗体

• 批准号: 6293630
• 负责人: Kevin John Whaley
• 金额: $ 24.85万
• 依托单位: EPICYTE PHARMACEUTICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-15 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6293630
• 关键词: antiviral antibody; cell line; genetically modified animals; human papillomavirus; immunologic substance development /preparation; immunopharmacology; immunotherapy; laboratory mouse; monoclonal antibody; passive immunization; plant extracts; vagina; viruslike particle

DESCRIPTION (Verbatim from Applicant's Abstract): An evolving strategy for the prevention of sexually transmitted diseases is the development of broad spectrum vaginal microbicides. Many of these microbicides (e.g. detergents like nonoxynol-9) have mechanisms of action that are not limited to specific pathogens and may have deleterious effects on host cells or may compromise epithelial integrity. In contrast, antibodies are naturally occurring microbicides that are highly specific, yet, by working in combination with other antibodies, can achieve broad spectrum protection without injuring healthy tissues or commensal organisms. The specificity of antibodies together with their versatility make them leading microbicide candidates. The objective of this project is to develop antibodies specific for human papillomavirus (HPV-16), a sexually transmitted pathogen associated with cervical cancer, that can be combined with antibodies against other STD pathogens already being produced in corn (plantibodies) by EPIcyte. The first specific aim is to generate a panel of anti-HPV human monoclonal antibodies by immunizing transgenic mice with HPV virus-like particles (VLPs). These human monoclonals will be tested for in vitro neutralization and in vivo efficacy in the second specific aim. The phase II proposal will include production of select anti-HPV human monoclonals in plant, and clinical evaluation of these plantibodies. PROPOSED COMMERCIAL APPLICATION: Antibody-based technology is now coming to fruition for systemic therapeutics, but the untapped commercial applications for antibodies are in mucosal prevention. A vaginal microbicide is one important application for mucosal antibodies; antibody technology is so flexible that it is readily extended to other reproductive health applications or to the prevention of diseases by pathogens at other mucosal sites. The production of antibodies in plant as plantibodies will enable this technology to meet cost and capacity demands.

描述（来自申请人摘要的逐字）： 预防性病是发展广泛的 广谱阴道杀菌剂。许多这些杀微生物剂（例如洗涤剂， 壬苯醇醚-9）具有不限于特定的作用机制， 病原体，并可能对宿主细胞产生有害影响或可能损害 上皮完整性相反，抗体是天然存在的， 杀微生物剂是高度特异性的，然而，通过与 其他抗体，可以实现广谱保护而不伤害 健康的组织或微生物。抗体的特异性 它们的多功能性使它们成为领先的杀微生物剂候选者。 本项目的目标是开发针对人类的特异性抗体， 乳头状瘤病毒（HPV-16），一种性传播的病原体， 宫颈癌，可以与其他性病抗体结合 已经在玉米中产生的病原体（植物体）。第一 具体目的是通过以下步骤产生一组抗HPV人单克隆抗体： 用HPV病毒样颗粒（VLP）免疫转基因小鼠。这些人类 将测试单克隆抗体的体外中和和体内功效， 第二个具体目标。第二阶段的建议将包括生产 在植物中筛选抗HPV人源性单克隆抗体，并对其进行临床评价 植物体 拟定商业应用： 基于抗体的技术现在正在实现全身治疗，但 抗体尚未开发的商业应用是粘膜预防。 阴道 杀微生物剂是粘膜抗体的一个重要应用;抗体技术是 灵活性，易于扩展到其他生殖健康应用或预防 其他粘膜部位的病原体引起的疾病。 在植物中产生抗体， plantibodies将使这项技术能够满足成本和容量需求。