STTR Phase I: A platform for the rapid discovery of human antibodies as therapeutics for infectious disease (COVID-19)

STTR 第一阶段：快速发现人类抗体作为传染病治疗药物的平台（COVID-19）

• 批准号: 2036233
• 负责人: Bradley Poulsen
• 金额: $ 25.56万
• 依托单位: Altigg Therapeutics, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2036233&HistoricalAwards=false
• 关键词: STTR; Phase; platform; rapid; discovery

The broader impacts of this Small Business Technology Transfer (STTR) Phase I project are to establish a novel and rapid drug-discovery platform aimed at infectious diseases. An opportunity is to tap into an unexplored diversity of human antibodies and develop them into therapies. This technology aims to identify drug candidates and select therapeutic candidates quickly. The established platform will be poised to counter emerging outbreaks and existing stubborn pathogen such as drug-resistant bacteria. The priority is the current COVID-19 pandemic, but this can be expanded to other potential pathogens. This STTR Phase I project will establish a novel discovery platform of human antibody therapeutics to counter infectious diseases. The rise of devastating new pathogens, such as SARS-CoV-2 (COVID-19) and antibiotic-resistant bacteria, calls for alternative and rapid therapeutic approaches. Traditional therapeutic antibody development generally involves animal models or/and affinity selection systems. They are expensive and lengthy, requiring multiple steps, including humanization, to mitigate immune neutralization. The proposed method identifies human antibodies (IgG) targeting a pathogen of interest in only nine days. The approach also capitalizes on an unexplored diversity of human antibodies. The pipeline begins with a collection of donor cells containing plasmablasts, which are modified to capture own-secreted IgG allowing for the enrichment of the relevant cells. The cells are sorted in single wells in a high throughput fashion. The process continues with high throughput cloning, antibody expression, and a preliminary binding and neutralization screen. The pipeline lasts nine days from cells to the initial binding screen, identifying hundreds of antibodies of varying characteristics. The initial screen is followed by further tests of binding kinetics and neutralization assays.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个小企业技术转让（STTR）第一阶段项目的更广泛影响是建立一个针对传染病的新型快速药物发现平台。一个机会是利用人类抗体的未开发的多样性，并将其开发成治疗方法。该技术旨在快速识别候选药物并选择治疗候选药物。已建立的平台将随时准备应对新出现的疫情和现有的顽固病原体，如耐药细菌。当前的重点是COVID-19大流行，但这可以扩展到其他潜在病原体。该STTR I期项目将建立一个新的人类抗体疗法发现平台，以对抗感染性疾病。毁灭性的新病原体，如SARS-CoV-2（COVID-19）和耐药性细菌的出现，要求采用替代和快速的治疗方法。传统的治疗性抗体开发通常涉及动物模型或/和亲和选择系统。它们昂贵且耗时，需要多个步骤，包括人源化，以减轻免疫中和。所提出的方法仅在9天内就能识别出针对感兴趣病原体的人抗体（IgG）。该方法还利用了人类抗体的未开发多样性。该管道从收集含有浆母细胞的供体细胞开始，浆母细胞被修饰以捕获自身分泌的IgG，从而允许富集相关细胞。以高通量方式在单个威尔斯孔中分选细胞。该过程继续进行高通量克隆、抗体表达以及初步结合和中和筛选。从细胞到最初的结合筛选，这条管道持续了9天，识别了数百种不同特性的抗体。初步筛选之后是结合动力学和中和试验的进一步测试。该奖项反映了NSF的法定使命，并且通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。