Scheme: Industry Fellowship
Organisation: University of Kent at Canterbury
Dates: Nov 2013-Oct 2017
Summary: Many drugs in the clinic and in development are now protein based drugs that must be expressed from cultured cell systems. Approximately half of these proteins are made in cultured mammalian cell lines of which the Chinese hamster ovary (CHO) cell line is the major cell line utilized commercially. The rapid development of highly productive cell lines (those that make large amount sof the required protein ina functionally active state) is key to both reducing cost of goods for therapeutic protein manufacture and getting more molecules into first-in-human studies faster. Despite many advances in the generation of high producing recombinant mammalian cell lines, research and cell line development is often slowed or hindered by the inherent heterogeneity of mammalian cell populations. This heterogeneity is useful in that it allows the isolation of cell lines with different attributes, but also a hindrance in that large numbers of cell lines need to be assessed to ensure a suitable cell line, capable of producing high concentrations of the desired protein drug in large volume bioreactors, is isolated. Here we have developed a method based upon mass spectrometry to generate a unique fingerprint of each cell line early in the development process and relate that to the amount of product the cell line produces. We have shown that using this technology we are able to select cell lines that are good recombinant biotherapeutic protein producers early in the cell line development process. A major advantage of the approach is the potential reduction of time to development of a production cell line which will allow faster manufacturing of these expensive protein drugs, allow faster first-in-human studies to be achieved and potentially reduce manufacturing costs and hence the cost of goods. The technology is now being applied to other settings, including authentication of cell lines, characterization of cancer cell lines and to provide markers of stem cells.