Engineering challenges in personalised cell therapies: applying fundamental engineering, ultra scale-down design and experimental flow dynamics approaches for the design of novel cell culture platforms
This PhD is funded as part of the Future Targeted Healthcare Manufacturing Hub, based at UCL Biochemical Engineering and involving leading academics across the UK as Spokes. The Hub is supported by a large number of the leading manufacturers and suppliers in the biotherapeutics industry and non-governmental associations. The Hub was launched in June 2017 and is funded for a period of 7 years (2017-2024). It will address the manufacturing, business and regulatory challenges to ensure that new targeted biological medicines can be developed quickly and manufactured at a cost affordable to society. One case study within the Hub focuses on
personalised cell therapy medicines, with a specific focus on T-cells for acute Lymphoblastic Leukaemia. Current process is long, labour-intensive, prone to contamination and characterised by large patient-to-patient variability. Novel bioprocesses, analytics and control algorithms are needed that enable robust, safe and cost-effective manufacturing and formulation of personalised cell medicines. This will provide the flexibility and speed to produce medicines for small patient populations or individuals in response to clinical diagnostic data.
In current personalised medicine protocols T-cells are harvested from a patient, manipulated and delivered back to the patient, requiring a high level of process control, sound and in-depth knowledge of the microenvironment at critical process steps and understanding of the cell’s response to a range of physical, chemical and metabolic shifts. A closed single-use bioreactor solution (either stirred SUBs or rocked bags) offer an interesting opportunity for the expansion of Tcells by minimizing the risk of cross contamination with other patients’ cells, or with other agents during handling, and by ensuring compliance with regulatory requirements. Rigorous engineering characterisation of existing and newly designed bioreactors is crucial due to the unique scalability requirements of cellular immunotherapies.
Project summary This proposal will establish a rigorous fundamental engineering understanding of the impact of fluid dynamics on multiple process steps towards safer and more robust personalised medicine manufacture and will enable the design of ultra-scale down devices that will speed the development of the next generation processing while improving yields and reducing cost of therapies. The engineering understanding will be used to design a portfolio of novel ultra scaledown tools to evaluate and model the effect of 3D shear environment of T-cells expansion and subsequent process steps. The project will be guided by an iterative design thought process, from the establishment of objectives and specification criteria, through to synthesis, analysis, fabrication, testing and end-user evaluation. A portfolio of USD tools mimicking critical process interactions would be invaluable to optimise the process at a small scale, targeting key cost drivers, thus establishing a more robust process from the start and allowing for savings at later stages of development. Engineering characterisation experiments will be based on the use of laser-based techniques, high speed camera imaging and automated image analysis. A Particle Image Velocimetry (PIV) system will be used to obtain information on flow pattern, presence of stagnant areas, mean and turbulent velocity characteristics and extent of laminar/transitional flow at specific locations. Macromixing information, obtained under a range of industrially relevant operating conditions, will constitute a basis for developing scale translation models and provide a thorough and complete insight of the mechanism of operation from the engineering/fluid dynamics viewpoint. The engineering insight will inform the design of the subsequent T-cells cultivation experiments.
Application The application deadline is 16 August 2019. To apply, please send your CV and cover letter to Laura Nagle: [Email Address Removed]