Project One: Development and Testing of the HCA IVR

项目一：HCA IVR的开发与测试

• 批准号: 9548350
• 负责人: Deborah J Anderson
• 金额: $ 79.02万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-13 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9548350
• 关键词: Antibodies; Antigens; Biological Assay; Biological Products; Clinical Trials; Contraceptive Agents; Contraceptive methods; Development; Engineering; Epithelial; Epithelium; Evaluation; Goals; Human; IgG1; Industrialization; Inflammation; Lead; Macaca; Modeling; Performance; Preclinical Testing; Prevention; Safety; Sexually Transmitted Diseases; Sperm Agglutination; Sperm Motility; Technology; Testing; Toxic effect; Vagina; Vaginal Ring; Variant; Work; base; contraceptive efficacy; design; human monoclonal antibodies; male; novel; prevent; prototype; reproductive tract; sperm cell; sperm function

Project 1 is the main contraceptive development project for the BUSM CRC. The overarching goal of Project 1 is to deliver a Human Contraceptive Antibody (HCA) and prototype HCA-intravaginal ring (HCA-IVR) that are ready for human clinical trials. In the first year of the project we will work closely with Mapp Biopharmaceutical (Antibody Industrialization Core) to test HCA IgG1 and engineered variants of HCA for contraceptive efficacy in sperm agglutination and motility assays. Based on the results of these studies, we will select lead HCA candidates showing maximum efficacy to undergo further testing in additional sperm function assays assessment for toxicity/inflammation in a human vaginal epithelium model. Our lead HCA (HCA*) will be selected based on performance in sperm function tests and the safety evaluation. In subsequent years of the project, HCA* will be manufactured by the Antibody Industrialization Core and incorporated into an IVR specifically designed for the purpose of sustained release of HCA*. The HCA*-IVR will undergo preclinical testing in a macaque model to assess safety, PK, ex vivo efficacy and antibody and sperm distribution in the lower genital tract.

项目1是BUSM CRC的主要避孕开发项目。总体目标 项目1的作用是提供人类避孕抗体（HCA）和原型HCA内膜 为人类临床试验准备的环（HCA-IVR）。在项目的第一年，我们将工作 与MAPP生物药物（抗体工业化核心）紧密接近测试HCA IgG1和 HCA的工程变体用于精子凝集和运动分析中的避孕功效。 根据这些研究的结果，我们将选择显示最大的HCA候选者 在其他精子功能分析评估中进行进一步测试的功效 人类阴道上皮模型中的毒性/炎症。我们的铅HCA（HCA*）将被选中 基于精子功能测试的性能和安全评估。随后的几年 该项目HCA*将由抗体工业化核心制造并成立 进入专门设计的IVR，目的是持续释放HCA*。 HCA*-IVR 将在猕猴模型中进行临床前测试，以评估安全性，PK，离体功效和 下生殖道中的抗体和精子分布。