SBIR Phase I: Automated Closed Systems for Manufacturing Autologous Dendritic Cell Therapies

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is in the development of new technologies to manufacture personalized therapies for cancer and other diseases that are based on a patient's own cells. Such therapies have shown remarkable success in recent years, however, manufacturing these therapies is challenging because mass production techniques cannot be employed when each patient receives a unique therapy. Indeed, for therapies based on dendritic cells, which are an important part of the human immune system, there are no manufacturing systems currently available that can perform all of the required steps. This project will address this major unmet need by leveraging advanced concepts in engineering and biology to design an integrated system for cost-effective manufacturing of dendritic cell therapies. Given the large number of personalized cell-based therapies currently in clinical trials, and recently approved therapies, such a system is expected to address a major societal need and have significant commercial potential. This SBIR Phase I project proposes to develop a manufacturing system to cover the steps involved in the manufacturing of autologous dendritic cell therapies. Because of the low abundance of these cells in blood, dendritic cells are typically generated from blood-derived monocytes. Following differentiation of monocytes into dendritic cells, these cells are then matured and stimulated with tumor-specific antigens. These steps represent discrete unit operations that require a system capable of handling both adherent and non-adherent cell types, different reagents for each step, and the ability to transition from one step to another with minimal loss of cells. Further, all steps must be performed in a disposable single-use enclosure. In order to achieve automation and integration of these steps, the proposed system will leverage innovations in perfusion-based dendritic cell culture and novel and cost-effective bioreactor design strategies. A combination of computational modeling and rapid-prototyping techniques will be employed for rapid iteration of prototypes and testing with potential users involved in therapeutic development. Successful completion of this project will result in feasibility demonstration of an integrated manufacturing system developed with significant end user feedback. 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.