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

这个小企业创新研究第一阶段项目的更广泛的影响/商业潜力是开发一种使用SARS-CoV-2刺突蛋白(Sp)的特定免疫保护性细胞疗法，以增强对新冠肺炎的免疫力，特别是在合并疾病时。持久的竞争优势反映了新型冠状病毒Sp的免疫细胞工程是基于干细胞的免疫疗法(SCT)的新技术进步，用于治疗病毒疾病、糖尿病、自身免疫性疾病或癌症。使用针对SARS-CoV-2或新病毒株的SCT将预防新冠肺炎和感染后并发症，降低未来大流行的机会，并加强地方和国家经济。这个小型企业创新研究(SBIR)第一阶段项目将开发一种“DC-COV19”探测系统，以根除导致美国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新冠肺炎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疫苗针对的是中和抗体，但只依赖内源性T细胞的产生。主要差距：新冠肺炎患者表现出T细胞数量和功能的显著减少，需要强有力的疫苗或免疫治疗策略来提高SARS-CoV-2特异性CD_4~+和CD_8~+T细胞。NeyroblastGX LLC(NGL)计划开发一种从树突状细胞(DC)中提取的探针，该树突状细胞(DC)来自已建立的转基因人类胚胎干细胞(HESC)，该细胞转染SARS-CoV-2刺突蛋白(Sp)。这种“DC-COV19”探针将被用来在体外产生大量具有功能的SARS-CoV-2特异性CD4+和CD8+T细胞。自体免疫T细胞将被移植到新冠肺炎患者体内，作为一种快速而有力的基于T细胞的适应性免疫疗法。NGL与世界一流的免疫学家和临床医生合作开发了几种Sp结构，这些Sp结构经过改造后可以转染树突状细胞，选择性地激活SARS-CoV-2特异性的CD4+和CD8+T细胞，以对抗CoVID-19。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.