Process development for improved Car-t production utilizing an automated single use perfusion stirred-tank bioreactor

Ex vivo genetically-modified cellular immunotherapies, such as chimeric antigen receptor T-cells (CAR-T), have generated significant clinical and commercial outcomes due to their unparalleled response rates against refractory/relapsed blood cancers. However, the development and manufacture of these advanced therapies face a number of translational bottlenecks that must be addressed to ensure long-term commercial viability. The cost and variability associated with these personalized advanced therapies presents a critical manufacturing and translational challenge. Due to the nature of cell therapies, single-use technologies are typically used for their production. This work demonstrates the importance of determining critical manufacturing process parameters using single-use technologies and incorporating automation into the process. The work builds off of previous proof of concept work completed in the group for the production of CAR-T cells in automated, stirred tank, single-use ambr250® bioreactors. These follow-on experiments utilize concepts of quality by design and design of experiments (DoE) to systematically determine the impact of process parameters on CAR-T production. Please click Additional Files below to see the full abstract