Immune Tolerance Network

免疫耐受网络

• 批准号: 10493548
• 负责人: GERALD T NEPOM
• 金额: $ 483.12万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-31 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10493548
• 关键词: 2019-nCoV; Address; Antibody Therapy; Antiviral Agents; Antiviral Therapy; CD14 gene; COVID-19; COVID-19 pandemic; COVID-19 patient; Cardiac; Caring; Cells; Cessation of life; Dendritic Cells; Disease; Event; Generations; Healthcare Systems; Immune; Immune Tolerance; Inflammation; Inflammatory Response; Innate Immune System; Intensive Care; Kidney; Length of Stay; Monoclonal Antibodies; Organ failure; Patients; Pattern recognition receptor; Production; Randomized Controlled Trials; Recovery; Resolution; Respiratory Disease; Safety; Severities; Speed; Testing; Time; Tissues; Vaccines; Viral; Virus; Virus Diseases; care outcomes; clinical center; improved; improved outcome; macrophage; mortality; nasal swab; novel; novel strategies; organ injury; programs; randomized trial; remdesivir; respiratory; systemic inflammatory response; treatment strategy

Project Summary/Abstract: Anti CD14 (CaTT) The SARS-CoV-2 pandemic continues to spread around the world, causing widespread illness with significant mortality, overburdening health care systems and disrupting the global economy. Severe illness is caused by viral infection of host cells leading to the generation of secondary inflammatory responses that cause serious organ injury. We propose to test a novel treatment that will add to antiviral therapy by blunting the host innate immune inflammatory response to virally infected host cells using IC14, a specific blocking monoclonal antibody to the CD14 pattern recognition receptor on macrophages, dendritic cells and other cells of the innate immune system. In combination with a primary antiviral drug (e.g. remdesivir), this treatment strategy should reduce host inflammatory responses and speed resolution of illness. The primary hypothesis is that inhibiting the CD14 pattern recognition receptor will reduce the intensity of deleterious host inflammatory responses to the SARS-CoV-2 virus and secondary tissue damage and improve outcomes in patients with COVID-19 illness. We will conduct a multicenter randomized controlled trial in 300 patients in 15 US clinical centers in order to determine the efficacy and safety of IC14 in patients hospitalized with respiratory disease due to SARS-CoV-2. In Aim 1 we will determine whether IC14 improves the time to resolution of disease using an eight-point ordinal scale. In Aim 2 we will determine whether IC14 reduces the need for high level respiratory support, including ICU care. In Aim 3 we will determine whether IC14 reduces the severity of systemic inflammation and the recovery of virus in nasal swabs. Overall, this program will determine whether treatment with IC14 is an effective new approach to lessen systemic inflammation and organ injury triggered by the SARS-CoV-2 virus and improves outcomes in patients hospitalized with COVID-19 illness.

项目总结/摘要：抗 CD14 (CaTT) SARS-CoV-2 大流行继续在世界各地蔓延，造成广泛的疾病 死亡率很高，医疗保健系统负担过重，并扰乱了全球 经济。严重疾病是由宿主细胞的病毒感染导致产生 继发性炎症反应会导致严重的器官损伤。我们建议测试一本小说 通过削弱宿主先天免疫炎症来增加抗病毒治疗的治疗 使用 IC14（一种针对病毒感染的特异性阻断单克隆抗体）对病毒感染的宿主细胞做出反应 巨噬细胞、树突状细胞和其他先天细胞上的 CD14 模式识别受体 免疫系统。与主要抗病毒药物（例如瑞德西韦）联合使用，这种治疗 策略应减少宿主炎症反应并加速疾病的解决。这 主要假设是抑制 CD14 模式识别受体会降低 SARS-CoV-2 病毒有害宿主炎症反应的强度和继发性 组织损伤并改善 COVID-19 患者的预后。我们将进行一次 在美国 15 个临床中心对 300 名患者进行的多中心随机对照试验 确定 IC14 对因呼吸道疾病住院的患者的有效性和安全性 SARS-CoV-2。在目标 1 中，我们将确定 IC14 是否改善了解决问题的时间 使用八点顺序量表来评估疾病。在目标 2 中，我们将确定 IC14 是否减少 需要高水平的呼吸支持，包括 ICU 护理。在目标 3 中，我们将确定 IC14是否可以降低全身炎症的严重程度和鼻腔病毒的恢复 拭子。总体而言，该计划将确定 IC14 治疗是否是一种有效的新疗法 减轻 SARS-CoV-2 病毒引发的全身炎症和器官损伤的方法 并改善因 COVID-19 住院的患者的治疗结果。