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Training Network for the Immunotherapy of Cancer

Periodic Reporting for period 2 - IMMUTRAIN (Training Network for the Immunotherapy of Cancer)

Reporting period: 2017-12-01 to 2019-11-30

In the European Union, cancer is the leading cause of death and the overall incidence of cancer is still increasing. Currently, the prognostics indicate that 50 % of men and 40 % of women will be diagnosed with cancer during their lifetime. As a result of expanding efforts to improve cancer outcome, a main paradigm change is occurring in cancer therapy towards individualized medicine: The treatments do not target the tumor itself anymore but empower the immune system of the patients in order to support the development of an adequate immune response. The importance of immunotherapy has been highlighted by the prestigious Science journal as “breakthrough of the year 2013”, heralding its rising importance for the next decades. From 2014 to 2016 only, an estimated 39.000 publications have been released in this field. In the meanwhile, more than thirty compounds have been tested in phase III clinical trials. The private sector increasingly invests resources in immunotherapy of cancer.

Accordingly, the need for well-trained and skilled researchers in academia and industry is rapidly rising in this field. In response to this, the innovative training network of IMMUTRAIN has developed a pioneering program of education for young researchers in nine different European countries: It combines cutting edge research of antibody- based therapies with a range of courses enhancing knowledge and skills. Ten academic labs and five industrial research groups are involved in the program, bringing together experts in the fields of monoclonal antibodies, dendritic cells, T-cells and immunomodulatory nucleic acids as well as trainers specialized in the development of scientific management and related competencies.

Despite considerable advancements, many tumor entities still show resistance to classical antibody therapies. The scientific objective of IMMUTRAIN is to improve the efficacy of antibody-based therapies through combination with synergistic immunotherapeutic approaches. Hence, the research program compiles four different work packages:

1. Combination of antibodies with adoptive T cell transfer
2. New formulations and combinations of antibodies to activate immune cells
3. Combination of antibodies with dendritic cell therapy
4. Target discovery and validation for antibody combination therapies
"Significant progresses have been made in these few years. Work by our Early Stage Researchers has been able to identify tumor-secreted factors that favor immune suppression, uncover immune checkpoints, generate antibodies against new targets and ultimately, devise strategies to reactivate the immune system and reduce cancer growth and metastasis.

• 19 publications: 14 co-authored original papers and five reviews have been published among others in Science, and Nature.
• Partners have submitted two patents applications.

Immutrain organized four international conferences and six workshops in Munich, Milan and Copenhagen which covered the following topics:
- “Innate immunity meets tumor immunology“,
- “Advanced immune bio-imaging”,
- “Clinical oncology and combination treatment”
- ""Scientific writing, bioinformatics and career event""
- ""Transfer of technology and European patent; Immuno-oncology: heterogeneous cells battling in the tumor microenvironment at Miltenyi Biotec Scientific Days""
- ""Diversity, science communication and work/life balance""
- ""Progress and challenges of Immune Therapy. Experience of the European Training Network Immutrain""
• 130 training sessions were dedicated to knowledge and methodologies and transferable skills. They also improved chances of cooperation and employment in industry and academy.
• 15 Early Stage Researchers have benefitted from the know-how of the network by completing research visits to other labs and by participating in the mentoring program."
• IMMUTRAIN pioneers doctoral training in immunotherapy of cancer as it is one of the first programs in Europe offering courses in this rapidly expanding research field.
• IMMUTRAIN enables synergies among leading scientific labs. It contributes to the defragmentation of European research landscape in the field. It combines academic with industrial research and brings together expertise from cell biology, protein chemistry, tumor immunology, medical oncology, gastroenterology and clinical pharmacology.
• IMMUTRAIN develops new strategies which bypass the limitations of therapies based on monoclonal, monospecific antibodies (mAb): While there is progress in immune activation, unwanted side effects still remain; even if mAb are used as drug carriers, they do not address the problem of drug resistance; powerful mAb-based strategies, for example using bispecific antibodies, are limited by a high toxicity.
• IMMUTRAIN researchers have provided proof-of-concept or research enabling reagent studies for enabling T cell therapy, multispecific immune cell targeting, vaccination boosting and immune system modulation for potential anti-cancer therapeutic agents. These advances will open the path for further preclinical development.
• Around 550 scientists and international speakers attended the conferences and workshops organized on European level.
• Conferences, lab visits and events organized at local levels attracted more than 30.000 persons from science, industry, healthcare, patients organisations and general audience.
Immutrain - Overview of the work package topics