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

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.