Expansion of T-Cells from an Apheresis Collection in an Automated Functionally Closed Hollow Fiber Bioreactor System

Objectives, benefits and challenges of bioreactor systems for the clinical-scale expansion of T lymphocyte cells

“…One commercial example of a hollow fibre-centred bioreactor system is the Terumo Quantum®. This system is capable of culturing T cells to a therapeutic dose within one single-use set in the system; it is capable of achieving 90-500 fold increase in cell numbers after an inoculation of 1x10 8 lymphocytes (Nankervis et al, 2018;Startz et al, 2016). The starting number of cells is therefore quite high in experiments with the Quantum® system, and starting material quality can be a challenge in adoptive transfer of T cells (Juliano et al, 2018;Levine et al, 2017).…”

“…Co-culture of T cells with polymer particles known as Dynabeads is frequently used for the activation step in hollow fibre, wave bag and stirred tank bioreactor formats (Costariol et al, 2019;Hami et al, 2004;Startz et al, 2016). For the hollow fibre format, the CD4+:CD8+ ratio produced by the dynabead-activation and Quantum®-expansion of T cells was highly dependent on the donor material (Startz et al, 2016). Most samples tended to favour proliferation of CD8+ cells; however, for one donor, the ratio was close to 1:1.…”

“…The Dynabeads used in those studies activated T cells through engagement of the TCR by CD3, and costimulation by CD28 receptors. This method is known to produce a different ratio of CD4+ to CD8+ T cells depending on the dose of beads used (Cheung et al, 2018;Li and Kurlander, 2010;Startz et al, 2016). It is clear that in order to generate a further understanding of the cell expansion process, the effect of T cell activation, which has many effects as discussed earlier, and the effect of bioreactor need to be separated.…”