The UK’s Centre for Cell, Gene and Tissue Therapeutics – part of University College London (UCL) - is looking to initiate a Phase I trial within the next year for its Mesenchymal Stem Cell (MSC) based lung cancer therapy.
Speaking at the Cell Therapy Manufacturing & Gene Therapy Congress in Brussels earlier this month, the Centre’s Head of ATMP GMP Quality Control, Owen Bain, said the project has the potential to lead to an ‘off the shelf’ allogeneic product.
And in order to create a manufacturing process for early development with the capability of being used in later stages of development, the academic organisation has set the challenge of “making the world’s largest cell bank.”
But in order to do this, Bain explained, the Centre examined at a few different options for manufacturing cells.
“We looked at stir-tank bioreactors, a hollow fiber bioreactor from Terumo, or just going down the route of huge cell stacks, but even at this scale a walk-in type incubator would probably only treat about three patients, and so it’s not really the technology that we wanted to use.”
The Centre opted instead for the closed-system Xpansion 200 Bioreactor from Pall Corporation containing stacked hydrophilized polystyrene radial plates. According to Bain, each 614cm2 plate creates a large surface area for cell growth despite a relatively small volume (22L).
“Even using quite conservative estimates to cell density we’re looking at two billion cells per run, based off using about 17,000 cell/cm2.”
To prepare for an upcoming Phase I trial, “we really need to manufacture cells over the scale of ten billion to start with and the Xpansion system really allows the scale-up of MSCs with quite a small footprint.”
But while Pall’s system promises high cell numbers in the upstream process, there are still a number of challenges to overcome before submitting the documentation for initial clinical trials, Bain said.
“The main thing is always going to be can we actually get the cell numbers we want to? Changing technologies lead to massively different hold times when harvesting, which can particularly impact your cell viability, so we really need to optimise our downstream processing.”
UCL is also using human platelet lysate (HPL) culture media, rather than the fetal bovine serum (FBS), recognised as the “gold standard in cell culture supplements.”
Bain said HPL gives comparable growth characteristics to the Centre’s studies with FBS, and importantly will not jeopardise manufacture if its therapies reach commercialisation.
“If an allogeneic cell therapy was to reach market that was using FBS, virtually straight away demand [for FBS] would outstrip supply. So at the moment we are going with human platelet lysate, and using a concentration of 5%.”