ANTI-HPV HUMAN MONOCLONALS FOR A VAGINAL MICROBICIDE

描述(逐字摘自申请者摘要)：一种演变的战略 防止性传播疾病的发展是广泛的 阴道杀微生物剂的光谱。其中许多杀微生物剂(例如洗涤剂，如 具有不限于特定的特定的作用机制 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，抗体是自然产生的。 具有高度特异性的杀微生物剂，但通过与 其他抗体，可实现广谱保护而不损伤 健康组织或共生生物体。抗体的特异性共同作用 它们的多功能性使它们成为领先的杀微生物剂候选者。 该项目的目标是开发针对人类的特异性抗体 乳头瘤病毒(HPV-16)，一种与 宫颈癌，可与其他STD抗体相结合 已经在玉米中产生的病原体(植物抗体)由EPI细胞产生。第一 其具体目的是通过以下方式产生一组抗HPV人类单抗 用人乳头瘤病毒样颗粒(VLP)免疫转基因小鼠。这些人类 单克隆体将在体外中和和体内效果测试 第二个具体目标。第二阶段的提案将包括生产 植物体内抗HPV人源单克隆的筛选及临床评价 植物体。 建议的商业应用： 基于抗体的技术现在正在为系统疗法开花结果，但 抗体尚未开发的商业应用是在粘膜预防方面。阴道 杀微生物剂是粘膜抗体的重要应用之一；抗体技术也是如此 灵活的是，它很容易扩展到其他生殖健康应用或预防 由其他粘膜部位的病原体引起的疾病。植物AS中抗体的产生 PlantiBody将使这项技术能够满足成本和容量需求。

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.