ANTIBODY THERAPY FOR STAPHYLOCOCUUS AUREUS INFECTIONS

金黄色葡萄球菌感染的抗体治疗

• 批准号: 6018191
• 负责人: Tibor P Keler
• 金额: $ 10万
• 依托单位: MEDAREX, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6018191
• 关键词: Staphylococcus aureus; Staphylococcus infection; affinity chromatography; antibody specificity; cell mediated lymphocytolysis test; drug resistance; enzyme linked immunosorbent assay; genetically modified animals; human tissue; hybridomas; immunological substance; immunotherapy; laboratory mouse; microorganism disease chemotherapy; monoclonal antibody; phagocytosis; surface antigens

The long term goal of the application is to develop a treatment for antibiotic-resistant Staphylococcus aureus infections using human monoclonal antibodies. Methicillan-resistant S. aureus (MRSA) are a major cause of nosocomial infections worldwide, and effective treatment of these infections is currently managed with a relatively toxic antibiotic, vancomycin. Evidence supporting the protective role of humoral immune responses to S. aureus infections has been documented by several groups. The recent availability of transgenic mice that produce fully mature human immunoglobulins (HuMab mice), allows for the straightforward development of high-affinity specific human antibodies. This phase I proposal specifically aims to generate a panel of hybridomas that secrete high affinity human monoclonal antibodies specific for S. aureus surface antigens. These antibodies will be evaluated alone and in combination with clinically relevant strains of S. aureus using in vitro phagocytosis and killing assays. The ultimate goal of the project is to develop several antibodies to be used in combination for prevention of S. aureus infections in high-risk groups, or for treatment of individuals with MRSA infections. PROPOSED COMMERCIAL APPLICATION Human antibodies developed in this project may lead to a safe and effective treatment for the prevention and treatment of Staphylococcus aureus infections in humans.

该申请的长期目标是开发一种使用人单克隆抗体治疗耐抗生素金黄色葡萄球菌感染的方法。 耐甲氧西林金黄色葡萄球菌 (MRSA) 是全世界医院感染的主要原因，目前使用毒性相对较大的抗生素万古霉素来有效治疗这些感染。 多个研究小组已经记录了支持体液免疫反应对金黄色葡萄球菌感染的保护作用的证据。 最近出现的可产生完全成熟的人免疫球蛋白的转基因小鼠（HuMab 小鼠），使得高亲和力特异性人抗体的直接开发成为可能。 该第一阶段提案的具体目标是产生一组杂交瘤，这些杂交瘤可分泌对金黄色葡萄球菌表面抗原具有特异性的高亲和力人单克隆抗体。 这些抗体将单独进行评估，并与临床相关的金黄色葡萄球菌菌株结合使用体外吞噬作用和杀伤试验进行评估。 该项目的最终目标是开发多种抗体，联合使用以预防高危人群的金黄色葡萄球菌感染，或治疗 MRSA 感染个体。拟议的商业应用该项目中开发的人类抗体可能会为预防和治疗人类金黄色葡萄球菌感染提供安全有效的治疗方法。