Expandable Bioreactor for the culture of immune cells

Abstract

Background & Aim With the recent successes of autologous immunotherapy, with 2 therapeutic products approved by the Food & Drugs Administration (FDA) since 2017 and more in the clinical pipeline, there is a need for cell and gene therapy companies to transition from lab scale production to mass manufacture. Traditionally, bioreactors have been routinely used in process development and scale up manufacturing of biologics. However, such bioreactor systems are not suitable for immunotherapy production as, beyond standard external factors such as shear stresses, immune cells are also sensitive to factors such as density and require cell-to-cell contact to proliferate well. Methods, Results & Conclusion A novel single use bioreactor for non-adherent cell culture has been developed in SIMTech (Patent Application WO2018/182533 A1) that allows for culturing cells at constant density while increasing volume of culture media to support cell proliferation. The bioreactor features two different chambers, one for media reserves and the other for cells. The two chambers are separated by a membrane that allow for fluidic exchange between these chambers. The cell chamber has a built-in expansion mechanism that can be adjusted as cells proliferate, thus allowing the user to adjust at any time point and maintain consistent culture density. The bioreactor has been validated with Jurkat cell line and T cells derived from commercial PBMCs with promising results; it was observed that the cultured cells exhibited high viability and selectivity. Jurkat cells had a 240-fold increase in cell number after 14 days in culture while T cells (from commercial PBMCs), had a 47-fold increase in cell number after 21 days in culture. A direct comparison study (1 bioreactor vs multiple 24-well plates for the same increase in cell number) also demonstrated a significant reduction in protocol steps and culture handling time. The bioreactor is currently being tested on donor PBMCs and other cell types, in collaborations with clinicians and cell therapy laboratories, in order to develop a GMP workflow for clinical use.