I-Corps: Chimeric Antigen Receptor T Cell Manufacturing for Cancer Therapies

The broader impact/commercial potential of this I-Corps project is the development of a centrifugal fluidized expansion bioreactor, i.e., a cell manufacturing device, that reduces the production time to grow immune cells for cancer treatment. Cancer immunotherapies have shown great promise and efficacy in clinical trial studies, with seven being approved by the Food and Drug Administration (FDA); However, manufacturing these cells remains a limiting factor in widespread adoption. Current FDA-approved therapies require up to 250 million immune cells per infusion, with costs for a single dose nearing $500,000. The current manufacturing limitations underscore the urgent need for innovation in cell manufacturing. Prior research with an animal model shows this solution can reduce the manufacturing time for cell therapies by 30% in comparison to the fastest technology on the market. Using this technology, manufacturing directors at biopharmaceutical companies may be able to save space in their facilities and save money on labor and cell culture resources while clinicians at cancer centers are able to treat patients at a faster rate. By addressing time and resource limitations, the technology has the potential to reduce the financial barrier to lifesaving cell therapies, increasing adoption by cancer patients. This I-Corps project is based on the development of a centrifugal fluidized expansion perfusion bioreactor prototype. The bioreactor streamlines the cell expansion process by balancing centrifugal forces with a continuous feed of fresh medium to remove inhibitory waste products and retain cells unlike current solutions. Early research has shown that immune cells from cattle can be expanded, and that the prototype can sustain high cell population densities over 100 million cells/mL, reducing manufacturing time from 7-14 days to 5 days, and maintaining cell growth at 95% of the maximum rate. Moreover, unlike current manufacturing equipment, the bioreactor fits easily on a standard lab bench and is entirely self-contained, with its housing acting as a standalone unit with air filters and ultraviolet-c sterilization—eliminating the need for multi-million dollar cleanrooms. Findings from prior research support the potential impact the device would have on scalability and accessibility of cancer 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.