SBIR Phase II:Clinical scale and testing of the first virus-free precision gene edited cell therapy for veterinary oncology

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._x000D_ _x000D_ 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._x000D_ _x000D_ 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.