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

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/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，以提高对COVID-19的免疫力，特别是对合并症的免疫力。持久的竞争优势反映了新型冠状病毒Sp作为干细胞免疫疗法（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的免疫细胞工程。使用SCT治疗SARS-CoV-2或新的病毒株将预防COVID-19和感染后并发症，减少未来大流行的机会，并加强地方和国民经济。这个小企业创新研究（SBIR）第一阶段项目将开发“DC-COV19”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（类似疫苗），以阻止或减少SARS-CoV-2感染。SARS-CoV-2疫苗靶向中和抗体，但仅依赖于内源性T细胞的产生。主要差距：COVID-19患者的T细胞数量和功能显著减少，需要强有力的疫苗或免疫治疗策略来增强sars - cov -2特异性CD4+和CD8+ T细胞。NeyroblastGX LLC （NGL）提出利用已建立的基因工程人胚胎干细胞（hESC）衍生的树突状细胞（dc）开发一种探针，该树突状细胞转染了SARS-CoV-2刺突蛋白（Sp）。这种“DC-COV19”探针将用于体外产生大量功能性sars - cov -2特异性CD4+和CD8+ T细胞。自体免疫T细胞将作为一种快速、强大的适应性T细胞免疫疗法转移到COVID-19患者体内。NGL与世界一流的免疫学家和临床医生合作，开发了几种Sp构建物，用于转染dc，以选择性地激活sars - cov -2特异性CD4+和CD8+ T细胞来对抗COVID-19。该奖项反映了美国国家科学基金会的法定使命，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。

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.