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FWF Emerging Fields grant for search of immunotherapy against childhood cancer

12 Mar 2024
The DART2OS team was awareded an FWF "Emerging Fields" grant. Left to right: Johannes Huppa, Sabine Taschner-Mandl, Johannes Zuber, Anna Obenauf, Michael Traxlmayr, Dietmar Rieder. Credit: FWF/Klaus Ranger

The Austrian Science Fund (FWF) has awarded a grant from its new Emerging Fields funding scheme to a project that will seek to develop a personalised immunotherapy for children suffering from osteosarcoma, an aggressive bone cancer. The project, led by Johannes Zuber and with participation of Anna Obenauf, will align a range of technologies and approaches established for research with a long-term clinical vision.

The bone cancer osteosarcoma affects more than 1100 children and adolescents per year in the European Union. In contrast to many other childhood cancers, the treatment of osteosarcoma has neither changed, nor improved much over the past 40 years. The Austrian Science Fund (FWF) has now awarded a grant from its new Emerging Fields funding scheme to an interdisciplinary group of scientists led by IMP senior group leader Johannes Zuber to utilise cutting-edge research technologies to develop a new type of cell-based immunotherapy for the treatment of osteosarcoma.

The project DART2OS aims to exploit an unusual feature of osteosarcoma. While most childhood cancers show relatively few genetic mutations, the chromosomes of osteosarcoma cells are typically broken and reshuffled in very complex ways. This has complicated the search for new therapies, but also comes with an opportunity: the reshuffling of chromosomes often leads to the formation of altered proteins that do not occur in normal cells and thus can be detected by our immune system. Specifically, T-cells can recognise pieces of such altered proteins on the cancer cell surface and then kill cancer cells very effectively. But due to the chromosome reshuffling, each osteosarcoma patient harbours different mutations and altered proteins, so cell-based immunotherapies require the engineering specific T cells for each individual patient. This is complicated and has never been tried before.

DART2OS will take advantage of cutting-edge technologies, several of which have so far only been applied in basic research. Using these new tools, the team will deeply characterise genetic mutations, altered proteins, and matching T cell receptors, and then use this information to engineer patient-specific T cells for therapy. In addition, the team will explore ways to enhance the activity of engineered T cells and prevent cancer cells from evading T cell attack.

“Personalised T cell therapies hold great promise for preventing and treating distant metastases, which are the main cause of death in osteosarcoma,” says Johannes Zuber. “Our central goal is to lay the scientific and logistical groundwork for such therapies. This would demonstrate that the engineering of personalised T cell therapeutics is feasible in a clinically applicable timeframe.”

The technologies used in this project will be as diverse as the people applying them: Johannes Zuber (IMP) will bring his expertise in functional genomics and cancer genetics to the table; Sabine Taschner-Mandl (St. Anna Children’s Cancer Research Institute) is a specialist for translational research and clinical diagnostics; Dietmar Rieder (University of Innsbruck) a leading bioinformatician with ample cancer genomics experience; Johannes Huppa (Medical University of Vienna) is an expert in immunology and T cell signalling; Michael Traxlmayr (BOKU University) is a leading protein engineer; and Anna Obenauf (IMP) specialises on tumour immunology and therapy resistance.

“For DART2OS, we have assembled a dream team to take cutting-edge research technologies from the lab to the clinic,” says Johannes Zuber. “In the long term, this could not only benefit osteosarcoma patients, but proof a concept that could be transferred to other cancers, too. It is fantastic that we could convince the FWF of the potential of this project and to fund this journey.”

Further reading
Austrian Science Fund (FWF) -

Project partners

Anna Obenauf (IMP) -
Johannes Huppa (Medical University of Vienna) -
Dietmar Rieder (University of Innsbruck) -
Sabine Taschner-Mandl (St. Anna Children’s Cancer Research Institute) -
Michael Traxlmayr (BOKU University) -
Johannes Zuber (IMP) -