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BIOTEK2021-Bioteknologi for verdiskaping

KSP: CellFit - T cells fit to fight cancer

Alternative title: CellFit: T -celler tilpasset for å bekjempe kreft

Awarded: NOK 22.5 mill.

The concept of using the immune system to fight cancer - immunotherapy - is based on stimulating T cells to kill cancer cells. To produce T-cell therapy, T-cells are extracted from the patient's blood. These cells are equipped with specific proteins called receptors, which enable the T cells to recognize the cancer cells. The modified T cells are grown in large numbers in the laboratory and returned to the patient's body where they find and kill the cancer cells. Clinical results with such therapy in solid tumor have been disappointing compared to its success in blood cancer. In order to improve the therapeutic effect and provide more cost-effective treatment, further development of the production methods is needed. There is a great need for knowledge about the factors required to produce clinically optimal T cells similar to the T cells normally trained in the body for a successful physiological immune response. Large-scale testing is needed to identify these factors. CellFit has an interdisciplinary approach that combines automated high-throughput screening technologies with clinical T-cell production and access to innovative reagents. We want to offer optimal cell products (more active, longer lasting in the body) and processes (more efficient, more streamlined). High throughput screening methods are used today to identify targets for T cell therapy, but not to optimize the production process. Newly developed screening systems will enable rapid evaluation of T cell cancer cell killing efficacy and other desired properties. The combined expertise of SINTEF, Oslo University Hospital and Thermo Fisher in high throughput screening, cell therapy production and new reagent development will provide new innovative screening methods, improved cell products and processes that can be easily used to improve therapy and clinical outcome. In collaboration with the Oslo Cancer Cluster, we will ensure outreach and knowledge sharing to promote responsible research and innovation.

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.

Funding scheme:

BIOTEK2021-Bioteknologi for verdiskaping