Immunotherapy and the CellFit Project: Towards More Effective T-Cell Treatments
Immunotherapy, which harnesses the body’s own immune system to fight cancer, is based on activating T cells to attack cancer cells. In developing T-cell therapy, T-cells are isolated from the patient’s blood and equipped with specific receptors—proteins that enable them to recognize and eliminate cancer cells. These modified T-cells are then expanded in large numbers in the laboratory and returned to the patient, where they seek out and destroy cancer cells.
While T-cell therapy has shown promising results against blood cancers, its effectiveness against solid tumours has been limited. To increase therapeutic impact and reduce costs, further development of production methods is essential. There is a significant need for knowledge about which factors produce T cells with optimal functionality—cells that resemble those naturally formed in the body to ensure a robust immune response. Large-scale testing is crucial to identify these factors.
The CellFit Project takes an interdisciplinary approach:SINTEF contributes automated screening technologies, Oslo University Hospital (OUS) handles T-cell production and characterization, Thermo Fisher provides innovative reagents.
The goal is to develop cell products that are more active and persistent in the body, while optimizing production processes for efficiency and scalability.
Traditionally, high-throughput screening has been used to identify targets for T-cell therapy, but not to improve the production process itself. In the CellFit project, we have applied screening systems to rapidly evaluate desired T-cell properties, such as stem cell-like phenotypes, favourable metabolism, and enhanced cancer-killing ability. Through collaboration with Oslo Cancer Cluster (OCC), we have ensured effective knowledge sharing via workshops and a symposium, where we presented progress to academia, industry, and patient organizations.
Results achieved in the project:
• Established a T-cell screening platform
• Screening of a large number of reagents, including culture media, cytokines, T-cell stimulants, and chemical compounds
• Development of high-throughput assays for cancer cell killing and metabolic analysis
• Immunoprofiling of produced T cells
• Validation of selected conditions at larger scale with multiple donors
Several conditions have yielded highly promising results for T-cell phenotype and function. Selected conditions are now being tested at larger scale to assess long-term efficacy in mouse models and patients. We have already produced large quantities of T cells and treated lymphoma models, and testing in mice with solid tumours is planned. To protect these new production methods, an invention disclosure has been submitted to Inven2.
To streamline analysis of extensive immunoprofiling data, we have partnered with Expert Analytics, which has developed a new software solution for more automated data processing. Further development of this tool will also benefit other projects involving large-scale immunoprofiling.
Achieved and anticipated outcomes
The project has fostered strong interdisciplinary collaboration between SINTEF, Oslo University Hospital, Thermo Fisher, and Expert Analytics, integrating expertise in screening technologies, process development, immunology, and data analytics. This collaboration has resulted in the development of new technical competencies among participants across all these areas. A robust screening platform for T-cell optimisation has been established, and promising production conditions have been validated at scale. Through workshops and symposiums involving academia, industry, and patient organizations, we have strengthened knowledge sharing and stakeholder engagement. Furthermore, research results have been applied by industry partners, process developers, and clinical environments to refine T-cell production processes.
We expect broader adoption of optimised T-cell production methods in both clinical and industrial settings, increased capacity for large-scale immunoprofiling and automated data analysis in future immunotherapy projects, and a strengthened innovation ecosystem through continued collaboration with Oslo Cancer Cluster and commercialisation via Inven2.
Achieved and Expected Impacts
Short-term societal impact: Accelerated development of more effective and persistent T-cell therapies, improving treatment options for cancer patients.
Long-term impact: Potential reduction in cancer mortality rates and healthcare costs through scalable, cost-efficient immunotherapy solutions. This progress could also create new business opportunities for biotech companies and suppliers of reagents and analytical tools.
Scientific impact: Increased knowledge in T-cell biology and production optimization, influencing future immunotherapy research and clinical practice. The results from the CellFit project will serve as a foundation for several follow-up projects emphasising identified T-cell characteristics. Two scientific publications are currently in preparation.
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.
