SMARTCell: Scalable Manufacture of Advanced Regenerative Therapeutics - Cell Therapies

The most significant healthcare challenge facing the UK is the unavoidable transition towards an older, ageing population, resulting in an increased demand for hospital and social care, complex medical interventions, spiralling costs and increased societal burden. The development of new, affordable and effective medicines will therefore be necessary to ensure we maintain and improve the standard of UK and global healthcare.

A new type of medicine, advanced cell and gene therapy (CGT), has recently emerged as a promising treatment option for previously incurable conditions. CGTs will form the next-generation of advanced medicines with the potential to improve UK health and wealth. Examples of CGTs include cellular immunotherapies. These are medicines which use genetically-engineered cells to target cancer cells. Chimeric antigen receptor natural killer cell therapies (CAR-NK) are an example of a cellular immunotherapy. Natural killer cells are a key immune cell type that fights infections in our bodies, however, we can genetically-engineer them to express a non-native protein (the CAR) which allows the NK-cells to target and eliminate blood cancer cells, an ability they only possess because of the non-native CAR protein. These gene-modified therapies have demonstrated remarkable clinical success and offer a revolutionary approach to treat patients who have failed every other treatment option (e.g. chemotherapy, bone marrow transplant) and are ultimately destined to die of their disease. However, this new treatment option has resulted in dramatic outcomes, with patients in complete remission for years after receiving the therapy. It has effectively cured patients of their cancer.

However, despite their clinical promise, approved immunotherapies suffer from high costs (>$350,000 per dose), poorly defined manufacturing processes and challenging gene engineering approaches involving the use of expensive and complex viruses as vehicles for gene delivery. Without significant manufacturing innovations, the promise of these transformative, curative therapies will not be realised, and they will remain inaccessible to the vast majority of patients that need them. The implications for UK health, wealth and well-being are profound.

My Fellowship focuses on establishing a scalable manufacturing process for CAR-NK therapies and demonstrating the first litre-scale production for CAR-NK cells. This will be achieved by creating an innovative and intelligent control strategy to improve the production process and increase the number of cells that can be manufactured. We will use scientific and engineering approaches to understand how the cellular environment can be made more conducive to encourage cell growth, specifically monitoring and controlling the environmental conditions (e.g. gases, nutrients, temperature, pH) to support optimal cell production. We will establish the process conditions and technologies that are required to grow and generate sufficient numbers of cells for clinical applications. We will also develop a new way to engineer the cells using an approach that doesn't require the use of viruses (a non-viral approach) which is based on mechanical and chemical methods.

My Fellowship research programme will support the industrial and clinical communities to deliver this next-generation of advanced medicines to treat patients in the UK and ensure these therapies are accessible to the patients that need them at a price that is affordable for the UK health system to bear. This will also support the development of the growing cell and gene therapy manufacturing industry in the UK and support economic activity in the high-growth biomanufacturing sector.