Genentech’s plasminogen activator Activase became the first human therapeutic product produced using CHO cells in 1987. Since then the cell line has become an expression system of choice for biomanufacturers and is used to make best-selling monoclonal antibodies Rituxan, Humira and Enbrel, to name a few.
But the future of cheap and efficient bioproduction lies away from CHO cell lines, according to Biogen’s VP of International Manufacturing Eliana Clark.
'Radical departure from the CHO platform'
Speaking at the Bioprocessing International (BPI) European summit in Amsterdam this week, she said her firm has been looking at a “radical departure from the CHO platform” through collaboration with the Massachusetts Institute of Technology (MIT).
“If you look at the future of the industry in the protein space, how do we really lower the cost of manufacturing to a place where we can actually make affordable medicines for people?” she asked.
“We did a lot of modelling in collaboration with MIT and we realised the CHO cell line won’t get us there. With CHO cells we get to a certain amount of output but if we want to get to a much better output then we will have to make a change.”
The research – funded in part by the Bill & Melinda Gates Foundation – has been looking at alternative hosts for the production of biopharmaceuticals including fungal (such as yeast and chytrids), algae (diatom) and trypanosome (leishmanial) systems.
“The selection had not only to do with getting the right output from a manufacturing point of view, but about quality,” she said. “We are looking at all sorts of things [first investigated as potential cell lines] 20-30 years ago, but now we really know how to engineer cell lines so we can make these hosts make proteins that look like human proteins.”
Exponential productivity, dramatic reduction in costs
These were also selected due to having good genomic characterisation, high fermentation performance, a known glycoengineering pathway and an ease of purification, she said.
And while there will only be incremental improvements in productivity and cost of CHO expression systems going forward, modern cell line engineering tools such as CRISPR could lead to exponential increases in output using these alternative systems.
Clark added the results of the studies will be published in Q3 2017 but told delegates “what we have learnt today is that we are able to secrete full length antibodies from all the [alternative] hosts, and we can engineer them to secrete monoclonal antibodies.”