BIOTEKNOLOGI-BIOTEKNOLOGI

The concept of using the immune system to fight cancer, known as immunotherapy, is based on activating T-cells to attack cancer cells. To develop T-cell therapy, T-cells are isolated from the patient’s blood and equipped with specific receptors – proteins that enable the T-cells to recognize and attack the cancer cells. These modified T-cells are then cultured in large numbers in the laboratory and reintroduced into the patient’s body, where they locate and kill the cancer cells. Despite promising results in blood cancers, T-cell therapy for solid tumours has been disappointing. To improve therapeutic efficacy and make treatment more cost-effective, further development of production methods is necessary. There is a significant need for increased knowledge about the factors required to produce clinically optimal T-cells, similar to those naturally trained in the body to ensure a successful immune response. Large-scale testing is necessary to identify these factors. The CellFit project takes an interdisciplinary approach, combining automated high-throughput screening technologies with clinical T-cell production and access to innovative reagents. Our goal is to offer improved cell products that are more active and persistent in the body, as well as to optimize production processes that are more efficient and streamlined. Currently, high-throughput screening is primarily used to identify targets for T-cell therapy, but not to optimize the production process itself. Through the development of new screening systems, we will enable rapid evaluation of T-cells' ability to kill cancer cells and achieve other desired characteristics. The combined expertise of SINTEF, Oslo University Hospital (OUS), and Thermo Fisher in high-throughput screening, cell therapy production, and reagent development will result in innovative screening methods, improved cell products, and efficient processes that can be quickly implemented to enhance therapy and clinical outcomes. In collaboration with Oslo Cancer Cluster, we will ensure effective information sharing and knowledge dissemination to promote responsible research and innovation. We have now established the screening platform at SINTEF, with immunoprofiling of produced T-cells at OUS. Additionally, SINTEF has set up tests to examine cancer cell killing in high-throughput format, and we can perform metabolic testing of the T cells. We have screened several of Thermo Fisher’s innovative reagents, including cell culture media, T-cell stimulants, and chemical compounds, and some of these conditions have shown very promising results. We are soon ready to test large-scale production to assess whether we can continue to produce T-cells that provide long-term effects in mouse models and patients. To streamline the analysis of immunoprofiling, we are collaborating with Expert Analytics, specialists in data processing, visualization, machine learning, and software development. Their solutions will be applicable to other projects that involve immunoprofiling with many markers. We have also organized several workshops with Oslo Cancer Cluster, where we have shared knowledge and progress with stakeholders and potential users from academia, industry, and patient organizations.

Clinical outcomes reported for solid tumour adoptive cell therapy have been disappointing compared to liquid cancers. To improve therapeutic efficacy and treatment cost-effectiveness which depend on long-term clinical outcome, T-cell manufacturing methods require development. Standard, non-optimal, formulae are currently used in manufacture and a great knowledge gap exists for which factors are required to produce clinically optimal T cells in an artificial in vitro expansion versus a successful physiological in vivo T cell response. Large-scale testing is required to identify these factors. By merging automated high-throughput screening technologies with clinical T-cell manufacturing and the access to innovative reagents we will provide significantly improved cellular products (more active and in vivo persistent) and processes (higher yields, more streamlined). Although high-throughput screening approaches are used to identify and select targets or antigens in T-cell therapy, no one is currently using these techniques to screen culture conditions to advance the T-cell manufacturing process. Developed screening systems will enable rapid evaluation of ex vivo T-cell efficacy by direct testing of 2D and 3D tumour-cell killing, T-cell phenotype and metabolism. T-cell therapy can be combined with e.g. checkpoint inhibitors or metabolic drugs in this screening to enable identification of useful treatment combinations for patient groups or single patients in a personalized medicine approach. The combined competencies of SINTEF and Oslo University Hospital, and Thermo Fisher within high-throughput screening, cellular therapy production and novel reagents will provide innovative new screening methods, improved cellular products and processes readily translated to improve clinical therapy and outcome. In collaboration with Oslo Cancer Cluster we will ensure public outreach and knowledge-sharing to foster responsible research and innovation.