Development of experimentally-integrated process models for adaptive CAR-T cell therapy manufacturing

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A new generation of gene-edited cell therapies have been developed which have the potential to cure certain aggressive types of cancer. Autolus, a leading biopharmaceutical company within this field, are genetically engineering patient's own immune cells (T-cells) in vitro to recognise and target cancerous cells. Following in vitro engineering, patient's T-cells express 'chimeric antigen receptors' (CARs) on their surface, which have been carefully constructed to allow the T-cells to by-pass cancerous cells' defence mechanisms. Recently two FDA approved autologous CAR-T therapies have shown remarkable clinical outcomes, with most patients receiving therapy in remission (some for 5 or more years post-administration).However, the costly, inherently variable, sub-optimal, manual, and open manufacturing processes limit patient accessibility to these transformative therapies. To resolve these manufacturing challenges, it is necessary to compensate for the inherent variation in patient starting material and optimise production. An adaptive production system which measures and adapts to in-process measurements in real-time can achieve this. Such a system will require relevant, experimentally-derived process models. However, the use of such models is limited due to lack of robust experimental data, tools to support a structured approach, the difficulty of realising computationally tractable (low parameter) yet realistic models, and the specialised skill sets required. This Industrial Fellowship will focus on establishing experimentally-driven process models for adaptive autologous CAR-T cell therapy manufacture with the aid of combined expertise and facilities at Autolus and University College London (UCL). The proposed project will enhance understanding of the CAR-T manufacturing process and product characteristics, as well as providing effective predictive in-process tools for process development. The Industrial Fellow will develop a specialised skillset that will be a valuable foundation for a future career in cell and gene therapies.