Cancer is one of the leading causes of mortality in the European Union. 50 % of men and 40 % of women will suffer this diagnosis during their life time and over 18 million new cases were reported for 2018 . Over the last years, immunotherapy – which uses a patient’s own immune system to fight tumours – has emerged as an important complement to standard treatments. Clinical implementation of immunotherapy has established T cells as efficient anti-cancer weapons if targeted by specific drugs. Further therapeutic utilization has recently come to a breakthrough: adoptive T cell therapy (ACT), collecting and transform-ing the patient’s own T cells to treat cancer. An estimated 753 different cell therapies are currently in development, of which 375 are in clinical trials world-wide . The global cell therapy market was valued at $2.70 billion in 2018 and is expected to reach $8.21 billion in 2025 . If European pharmaceutical compa-nies and research institutions are among the world leaders in basic and preclinical aspects of immunity including cell therapy development, clinical innovations and approvals in this field have been pioneered in other countries, especially in the USA and in China.
The generation of such ACT products is a complex but ill-defined process with limited harmonisa-tion across production and clinical studies even for the same indication. Cytokines are proteins re-sponsible for the growth and differentiation of T cells. Such cytokines are a central part of the generation procedure, whilst also playing a key role in the efficacy and safety of the cellular product. There is however a limited understanding as to which cytokines might lead to the best outcome on any of these steps.
T-OP targets a pioneering research question: how do cytokines influence therapeutic outcome of ACT products? The generation and application of a therapeutic cells is highly complex and therefore, we urgently need to gather European expertise from basic research to clinical implementation. T-OP will com-prehensively approach this issue by bringing together European experts in cancer research, tumour immu-nology, protein engineering and cellular therapies from eight leading academic research groups, four academic organisations of excellence, two large companies in pharmacy and biotechnology, two SME with highly specific expertise in ACT production and in bioinformatics and one regulatory authority. The scientific program of T-OP addresses the critical steps in cell therapy application where cytokines are expected to impact outcome (from cell isolation and production to treatment through engineering) along five work packages: WP1) impact of cytokines on generation and safety of therapeutic T cell product, WP2) use of cytokines to generate defined effector cells for ACT, WP3) impact of cytokine signalling incorporation in genetic engineering of T cells, WP4) role of cytokines in shaping T cell immunity and WP5) detrimental effects of cytokine signalling on ACT.
