Tetravalent Humanized Anti-ICAM for Rhinovirus Infection

描述(申请人提供)：感冒是最常见的 影响人类的疾病，70%的病例是由鼻病毒引起的 (HRV)。大多数HRV血清型与鼻腔上皮细胞上的ICAM-1结合 感染周期的第一步；因此阻止HRV结合 对ICAM-L应防止心率变异依附，从而防止或缩短 现有感冒的持续时间和症状减轻。一项人体临床试验 鼻腔注射抗ICAM-1全抗体可延缓 感冒发作最多2天，症状减轻50%，但未能 防止初次感染。目前已知抗体-细胞间黏附分子-L 解离率与HRV病毒粒子本身的解离率相似，表明 与病毒相比，抗体在功能亲和力上没有先天优势 占用可用的感受器。这些研究的目标是产生 使用高功能亲和力抗体的试剂和临床前数据 针对细胞间黏附分子-1的人类预防和治疗载体的构建 鼻病毒(HRV)感染。几种多价人源化抗体构建物 将在大肠杆菌中表达，并对保护效果进行评估 体外培养的敏感细胞。在这些研究中产生的数据将用于 支持人体临床试验。 建议的商业应用：不可用

DESCRIPTION (provided by applicant): The common cold is the most prevalent disease affecting humans, and 70 percent of cases are caused by rhinoviruses (HRV). The majority of HRV serotypes bind ICAM-1 on nasal epithelial cells as the initial step in the infectious cycle; therefore preventing HRV from binding to ICAM-l should prevent HRV attachment and thereby either prevent or shorten the duration and decrease symptoms of existing colds. A human clinical trial using intranasal administration of an anti-ICAM-1 whole antibody delayed the onset of colds by up to 2 days and decreased symptoms 50 percent but failed to prevent initial infection. It is now known that the antibody-ICAM-l dissociation rate is similar to that of the HRV virion itself indicating that the antibody has no innate advantage in functional affinity over the virus in occupying available receptors. The goal of these studies is to generate reagents and preclinical data using a high functional affinity antibody construct directed against ICAM-1 for the prevention and treatment of human rhinovirus (HRV) infections. Several multivalent, humanized antibody constructs will be expressed in E. coli, and evaluated for efficacy in protecting susceptible cells in vitro. The data generated in these studies will be used in support of human clinical trials. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE