Induced pluripotent stem cells (iPSCs) are a “starting material grail” for advanced therapies. That’s according to Sven Kili, chief development officer at CCRM, the Canadian regenerative medicine accelerator. Kili, who spoke about future trends in biomanufacturing at the London Biotechnology Show in May, argues that advanced therapies are on a long-term journey towards using iPSCs as their starting cells.
“You can treat more patients cost-effectively with allogeneic therapies manufactured from cells taken from healthy donors [than autologous therapies like CAR-T], but there’s still processing involved,” says Kili. “The next stage after that is using iPSCs as a starting material grail.”
According to Kili, autologous therapies have the disadvantage of only treating one patient per manufacturing lot–often someone whose cells may be poor quality because they have a genetic disease or have undergone extensive cancer treatments.
To improve the quality of starting materials, he maintains that companies are now moving towards allogeneic therapies with cells taken from healthy donors, with the challenge being to identify those whose cells are resilient to being expanded and engineered.
“We need to identify super-donors as they walk through the door of the apheresis unit where blood is collected,” he says. “And groups are beginning to work on that.”
Extensive engineering and processing
But these cells still need extensive engineering and processing, he points out, and the ‘holy grail’ is the iPSCs. These are a “blank template” of a cell, he explains, that can be easily engineered with a CAR, TCR or other relevant receptor for therapeutic use, including against tumors.
Moreover, he explains, iPSCs are easy to scale up to affordably treat diseases affecting tens of thousands of patients.
“They’re an almost unlimited source of cells that can be generated in a closed process, and the large bioreactors used can bring the cost of goods right down,” he says, adding that CCRM is probably the world leader in iPSC cell line generation.
“The challenge with iPSCs is, to create a final cell line, you have to run huge numbers of clones and spend a lot of time and costs on long-term validation work,” he says.
Regulators, for example, have been concerned about the risk of teratoma tumour formation from unstable clones and rightly expect companies to do extensive work on safety profiles.
“For companies starting up with even a $50 million investment, they just can’t afford to create an iPSC cell line. That’s why they often show proof-of-concept with autologous cells first,” he explains.
Keeping costs down
By investing money on iPSC cell line development and then licensing the cells to multiple companies, CCRM can keep costs down for the final users, he points out. Other trends in cell therapy manufacturing include increasing production speeds, treating huge numbers of patients, and maintaining machinery kept in hospitals for bedside manufacturing.
“As we move from treating rare orphan diseases to common conditions like sickle cell and onto diseases affecting hundreds of thousands of people each year, we need a fully automated process where cells go in one side and a product comes out the other,” he continues.
“I don’t see manufacturing at the bedside, next to the patient, as ready for prime time in the next five years as there are still lots of practical challenges. For example, what happens if there is an in-process issue or even the power is switched off at the wall? And who is ultimately responsible if there’s a manufacturing safety issue?”
