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

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is in the development of new technologies to manufacture personalized therapies for cancer and other diseases, based on a patient's own cells. Such therapies have shown tremendous potential in the treatment of previously intractable cancers. However, challenges in manufacturing these completely personalized therapies are a significant impediment to the ability to realize their full societal potential both in terms of therapeutic efficacy and cost. This project aims to remove major manufacturing barriers for therapies based on dendritic cells, which are an important part of the human immune system and can be modified to target specific diseases. No manufacturing systems currently available can perform all the required steps of manufacturing personalized dendritic cell therapies. This project will address this major unmet need by leveraging advanced concepts in engineering and biology to design an integrated system for cost-effective dendritic cell therapy manufacturing. Given the large number of personalized cell-based therapies currently in clinical trials and recently approved, such a system is expected to address a major societal need and have significant commercial potential. This SBIR Phase II project will advance to commercialization an advanced bioreactor system for closed-system manufacturing of autologous dendritic cell therapies. Multiple technological challenges must be overcome to automate and integrate the unit operations associated with the manufacturing of these therapies. Because of their low abundance in blood and tissue, dendritic cells are typically generated from leukapheresis-derived monocytes. Adherent monocytes must first be converted into nonadherent immature dendritic cells via incubation inIL4 and GM-CSF, prior to maturation and stimulation with tumor specific antigens. In order to achieve automation and integration of these steps on a single platform, the proposed system will build on successful Phase I work in perfusion-based dendritic cell culture that enables reduction of process steps associated with cytokine infusion and achievement of perfusion in a simple and cost-effective single-use bioreactor design. In addition, an agile product development methodology will be utilized in conjunction with computational modeling to rapidly and iteratively create prototypes and test them in the hands of potential customers. Feedback obtained from these users will be incorporated into the assembly of a pre-production beta system to be launched commercially at the end of Phase II. 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.