SBIR Phase I: Genetically Engineered Dendritic Cell to Activate SARS-CoV-2 Spike Protein specific-T Cell (COVID-19)

SBIR 第一阶段：基因工程树突状细胞激活 SARS-CoV-2 刺突蛋白特异性 T 细胞 (COVID-19)

• 批准号: 2051522
• 负责人: Aynun Begum
• 金额: $ 25.6万
• 依托单位: NEYROBLASTGX LLC
• 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 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2051522&HistoricalAwards=false
• 关键词: SBIR; Phase; Genetically; Engineered; Dendritic

The broader impact /commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to develop a specific immunoprotective cell therapy using the SARS-CoV-2 spike protein (Sp) to boost immunity against COVID-19, especially with comorbidities. A durable competitive advantage reflects immune cell engineering with novel coronavirus Sp as a new technological advancement for stem cell-based immunotherapy (SCT) to treat viral diseases, diabetes, autoimmune disorders, or cancer. Use of SCT against SARS-CoV-2 or new virus strains will prevent COVID-19 and post-infection complications, reduce the chance of future pandemics, and strengthen the local and national economy. This Small Business Innovative Research (SBIR) Phase I project will develop a "DC-COV19" probe system to eradicate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which killed more than 400,000 people in the United States. Our long-term goal is to develop a potent COVID-19 T cell-based immunotherapy (vaccine-like) for high-risk populations to stop or reduce SARS-CoV-2 infections. The SARS-CoV-2 vaccines target neutralizing antibodies but only rely on the endogenous production of T cells. Major Gap: COVID-19 patients showed a significant reduction in the number and function of T cells and required robust vaccine or immunotherapeutic strategies to boost SARS-CoV-2-specific CD4+ and CD8+ T cells. NeyroblastGX LLC (NGL) proposes to develop a probe from dendritic cells (DCs) derived from established genetically engineered human embryonic stem cells (hESC) transfected with SARS-CoV-2 spike protein (Sp). This "DC-COV19" probe will be used to produce high numbers of functional SARS-CoV-2-specific CD4+ and CD8+ T cells ex vivo. Autologous immune T cells will be transferred into COVID-19 patients as a rapid and robust adaptive T cell-based immunotherapy. NGL works with world-class immunologists and clinicians to develop several Sp constructs engineered to transfect DCs to selectively activate SARS-CoV-2-specific CD4+ and CD8+ T cells to fight COVID-19.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.

这项小型企业创新研究（SBIR）I期项目的更广泛影响/商业潜力是开发一种使用SARS-CoV-2刺突蛋白（Sp）的特异性免疫保护细胞疗法，以增强对COVID-19的免疫力，特别是合并症。持久的竞争优势反映了新型冠状病毒Sp的免疫细胞工程作为基于干细胞的免疫疗法（SCT）治疗病毒性疾病，糖尿病，自身免疫性疾病或癌症的新技术进步。针对SARS-CoV-2或新病毒株使用SCT将预防COVID-19和感染后并发症，减少未来大流行的机会，并加强地方和国家经济。 这项小型企业创新研究（SBIR）第一阶段项目将开发一种“DC-COV 19”探针系统，以根除在美国造成40多万人死亡的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。我们的长期目标是为高危人群开发一种有效的基于COVID-19 T细胞的免疫疗法（疫苗样），以阻止或减少SARS-CoV-2感染。SARS-CoV-2疫苗靶向中和抗体，但仅依赖于T细胞的内源性产生。 主要差距：COVID-19患者显示T细胞的数量和功能显著降低，需要强大的疫苗或免疫策略来增强SARS-CoV-2特异性CD 4+和CD 8 + T细胞。NeyroblastGX LLC（NGL）建议开发一种来自树突状细胞（DC）的探针，树突状细胞来源于已建立的基因工程人胚胎干细胞（hESC），转染了SARS-CoV-2刺突蛋白（Sp）。这种“DC-COV 19”探针将用于离体产生大量功能性SARS-CoV-2特异性CD 4+和CD 8 + T细胞。自体免疫T细胞将被转移到COVID-19患者体内，作为一种快速和强大的适应性T细胞免疫疗法。NGL与世界一流的免疫学家和临床医生合作开发了几种Sp构建体，这些构建体被设计用于抑制DC，以选择性地激活SARS-CoV-2特异性CD 4+和CD 8 + T细胞来对抗COVID-19。该奖项反映了NSF的法定使命，并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。