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的目的是提供人类避孕抗体（HCA）和原型HCA-阴道内 环（HCA-IVR），准备用于人体临床试验。在项目的第一年， 与Mapp Biopharmaceutical（抗体产业化核心）密切合作，检测HCA IgG 1， HCA的工程变体在精子凝集和活力测定中用于避孕功效。 根据这些研究的结果，我们会选出表现最佳的HCA候选人， 在额外的精子功能测定中进行进一步检测的有效性评估， 在人阴道上皮模型中的毒性/炎症。我们的领先HCA（HCA*）将被选中 基于精子功能测试和安全性评价的性能。在随后的几年里， 该项目HCA* 将由抗体工业化核心生产，并纳入 专门设计用于持续释放HCA* 的IVR。HCA*-IVR 将在猕猴模型中进行临床前试验，以评估安全性、PK、离体疗效和 抗体和精子在下生殖道的分布。