ANTI-C. DIFFICILE HUMAN MONOCLONALS FOR IMMUNOTHERAPY

滑稽。

• 批准号: 6831431
• 负责人: Larry Zeitlin
• 金额: $ 30万
• 依托单位: MAPP BIOPHARMACEUTICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831431
• 关键词: Clostridium difficile; antibiotics; antibody neutralization test; antibody specificity; bacterial toxins; biotechnology; chemical kinetics; clostridial infection; disease /disorder model; disease /disorder prevention /control; enzyme linked immunosorbent assay; epitope mapping; hamsters; immunoglobulin genes; immunologic substance development /preparation; immunotherapy; monoclonal antibody; nonhuman therapy evaluation; oral administration

DESCRIPTION (provided by applicant): Clostridium difficile associated disease (CDAD) is an important cause of morbidity in hospital and nursing home patients, and is being increasingly recognized as an important cause of mortality. The objective of this project is to produce human monoclonal antibodies (Mabs) for the prevention and therapy of CDAD. Human Mabs have been generated against the two toxins of C. difficile using transgenic mice containing human immunoglobulin gene loci. In the first specific aim, Mabs will be characterized for their toxin neutralizing activity in vitro, as well as their specificity and antigen binding kinetics. The most potent neutralizing Mabs with the most desirable toxin-binding kinetics will be selected for production in a hollow fiber system to generate sufficient quantities for in vivo experiments. The second specific aim will evaluate these Mabs in a hamster model of C. difficile infection. Oral administration of the Mabs will be tested for prophylactic and therapeutic efficacy against CDAD, and the most effective Mabs will be chosen for clinical development.

描述（由申请人提供）：艰难梭菌相关疾病（CDAD）是医院和养老院患者发病的重要原因，并且越来越被认为是导致死亡的重要原因。该项目的目标是生产用于预防和治疗CDAD的人单克隆抗体（mab）。利用含有人免疫球蛋白基因位点的转基因小鼠制备了针对艰难梭菌两种毒素的人单克隆抗体。在第一个特定的目的，单克隆抗体将表征其毒素中和活性在体外，以及它们的特异性和抗原结合动力学。将选择具有最理想毒素结合动力学的最有效中和单克隆抗体在中空纤维系统中生产，以产生足够数量的体内实验。第二个具体目标是在艰难梭菌感染的仓鼠模型中评估这些单克隆抗体。我们将测试口服单克隆抗体对CDAD的预防和治疗效果，并选择最有效的单克隆抗体进行临床开发。