SBIR-STTR Award

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is to advance a novel way to treat cancer. The proposed project will use of reprogrammed, living immune cells to recognize and destroy cancer. The technology developed here can be used for treatment of this disease in dogs, and ultimately for humans. The proposed project is focused on application of novel gene editing technology to the engineering of cell therapies and demonstrating the safety of the resultant therapeutic modality in canines. This therapeutic modality is a human T immune cell reprogrammed with a Chimeric Antigen Receptor engineered to bind to CD20 (chCAR20-T cells), a protein found on the surface of cancerous B cells. Identifying optimal gene delivery and gene editing conditions is a primary focus towards enhanced manufacturing of CAR-T cells without the use of a virus. These optimal methods will be used to generate doses of allogeneic chCAR20-T cells and tested against multiple lines of CD20+ canine cancers in order to confirm their cytotoxic activity. The final objective of this proposal is to transplant chCAR20-T cells into laboratory canines to prove safety in vivo. This manufacturing platform can be applied to the development of human cell therapies.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.

The broader impact of this Small Business Innovation Research (SBIR) Phase II project is the development of a commercially-ready cell engineering platform that will enable a curative therapy for cancer in the veterinary market. An estimated 250,000 dogs get B cell lymphoma every year. Chimeric Antigen Receptor (CAR)-T cell therapy offers hope for a treatment for this disease. The project platform for engineering CAR-T cell therapy at scale enables the generation of a potential new therapeutic product that is affordable on the veterinary market. The potential societal and commercial impacts of the project have the potential to translate successful therapies from dogs into human cancer care. This solution also offers a new model for the testing, development, and translation of novel CAR-T cell therapies for the human pharmaceutical industry, potentially resulting in benefits to humans as well as dogs.This project addresses a major bottleneck in the transition from research phase experimentation to clinical and commercial phase manufacturing. During the research phase, cell engineering platforms that process only 5,000,000 CAR-T cells per gene editing experiment or per manufacturing pilot study are sufficient. However, to expand to clinical scale manufacturing and to reach full market scale treatment of 50,000 dogs per year, the ability to make 50-500 doses per manufacturing run is required. Scaled electroporation systems can process up to 500,000,000 cells in a single experiment, a 100x increase from the research phase system. While the scale-up in cell programming reagents is expected to be 1:100, optimization is likely to be required to reach the same or better cell programming efficiencies, while the downstream outgrowth of this scale-up of cells also needs to be optimized in small scale bioreactors. The proposed engineering platform enables engineering of up to 500 doses of CAR-T cell therapy for under $500/dose at full scale.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.