Human Antibodies for Exposure/Protection from Anthrax

用于暴露/预防炭疽的人类抗体

• 批准号: 6739403
• 负责人: ANGRAY S KANG
• 金额: $ 39.99万
• 依托单位: AVANIR PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6739403
• 关键词: Bacillus anthracis; SCID mouse; anthrax; anthrax toxin; antibacterial antibody; biotechnology; bioterrorism /chemical warfare; clinical research; combination chemotherapy; disease /disorder model; drug interactions; exotoxins; human subject; immunologic substance development /preparation; laboratory rat; microorganism disease chemotherapy; monoclonal antibody; neutralizing antibody; nonhuman therapy evaluation; passive immunization; protein binding; recombinant proteins

DESCRIPTION (provided by applicant): Avanir Pharmaceuticals Inc., has developed a powerful platform for the rapid generation of high affinity fully human monoclonal antibodies that can be selected on their ability to neutralize anthrax toxin PA as exemplified by our lead candidate 8C1 (Kd 1.2 x10-12M, KinExA). Here we propose to continue the development of 8C1 as well as to isolate and characterize additional totally human monoclonal antibodies (MAbs) against B. anthracis exotoxin components protective antigen (PA) and lethal factor (LF). We will evaluate and characterize Mabs for affinity (using BiaCore and KinExA) and toxin neutralization (using an in vitro cell-based assay). Selected candidates will be further evaluated in a rodent animal model, using bolus challenge with recombinant anthrax toxins. By using multiple human donors, we will access a diverse a panel of antibodies and determine the optimal candidate(s) or combination of antibodies required to neutralize anthrax exotoxin in vivo. At the completion of this proposed study we will have candidates ready to enter the next stage of animal model evaluation. Testing candidates in live animal models with exposure to aerosolized anthrax spores are beyond the scope/budget of this study and would be the logical entry point for a phase II application. The following Specific Aims will be performed: -1: Generate a panel of high affinity fully human antibodies to PA and LF components of the tripartite B. anthracis exotoxin. -2: Evaluate and characterize MAbs binding and efficacy in an in vitro protection assay. -3: Determine protective efficacy in a rodent animal model, using bolus challenge with recombinant anthrax toxins.

描述（由申请人提供）：Avanir Pharmaceuticals Inc. 开发了一个强大的平台，用于快速生成高亲和力全人单克隆抗体，可以根据其中和炭疽毒素 PA 的能力进行选择，如我们的主要候选药物 8C1（Kd 1.2）所示。 x10-12M、KinExA）。在这里，我们建议继续开发 8C1，并分离和表征其他针对炭疽芽孢杆菌外毒素成分保护性抗原 (PA) 和致死因子 (LF) 的全人单克隆抗体 (MAb)。 我们将评估和表征 Mab 的亲和力（使用 BiaCore 和 KinExA）和毒素中和（使用体外基于细胞的测定）。选定的候选者将在啮齿动物模型中使用重组炭疽毒素进行推注攻击进行进一步评估。 通过使用多个人类供体，我们将获得一组不同的抗体，并确定体内中和炭疽外毒素所需的最佳候选抗体或抗体组合。在完成这项拟议的研究后，我们将让候选人准备好进入下一阶段的动物模型评估。在暴露于雾化炭疽孢子的活体动物模型中测试候选者超出了本研究的范围/预算，并且将是第二阶段应用的逻辑切入点。 将实现以下具体目标： -1：生成一组针对炭疽芽孢杆菌三方外毒素的 PA 和 LF 成分的高亲和力全人抗体。 -2：在体外保护测定中评估和表征 MAb 结合和功效。 -3：使用重组炭疽毒素进行推注攻击，确定啮齿动物模型的保护功效。