Ciro Chiappini – Senior Lecturer, Craniofacial & Regenerative Biology, King's College; Giovanna Lombardi – Professor, Peter Gorer Department of Immunobiology, King's College London
Abstract Text: In cell and gene therapy (CGT) manufacturing, large vessels known as bioreactors are used to support cell culture operations by providing a controlled microenvironment that mimics the physiological niche which the cells require to survive. The large fluidic volume of these vessels, which can often exceed 5 litres, poses issues which affect both the cost of the manufacturing process and the quality of the end product. An example of this is in chimeric antigen receptor (CAR) T-cell therapy manufacturing, whereby the multi-step, labour-intensive manufacturing process drives the high price-point of £280,000 per patient. GMP-grade reagents that are used in the manufacturing process, such as the lentivirus used for T-cell transduction, can account for as much as 50% of the materials costs. The large volume nature of bioreactors used in the process is often associated with low process efficiency and batch variability, resulting in a high-cost, heterogeneous product. While CAR T-cells are currently licensed for the treatment of haematological cancers, there is potential for the use of regulatory T-cells (Tregs) in the manufacturing process, to produce a CAR Treg therapy that can be used for the treatment of auto-inflammatory diseases. Here we present a closed-system, perfusion microfluidic bioreactor for the production of functional CAR Tregs from primary, human Tregs. The integration of a porous membrane allows continuous perfusion and transmembrane flow, which can be used to significantly increase Treg expansion and transduction efficiency, relative to standard plasticware.
