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IMMUTRAIN Report Summary

Project ID: 641549
Funded under: H2020-EU.1.3.1.

Periodic Reporting for period 1 - IMMUTRAIN (Training Network for the Immunotherapy of Cancer)

Reporting period: 2015-12-01 to 2017-11-30

Summary of the context and overall objectives of the project

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

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

• Immutrain organized two international conferences and two 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” and
- “Immunotherapy of cancer, current status and future prospects”.
• 76 training sessions were dedicated to knowledge and methodologies and transferable skills. They also improved chances of cooperation and employment in industry and academy. The young scientists benefit from the know-how of the network by completing research visits to other labs and by participating in the mentoring program.
• On the scientific side, significant progresses have been made. These include characterization of novel pathways that suppress an effective T cell response, new methodologies to activate immune cells, modulation of inhibitor expression on dendritic cells and the expression of single chain antibody fragments.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

• 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.
• 216 scientists and 64 international speakers attended the conferences and workshops organized on European level.
• Conferences, lab visits and exhibitions organized at local levels attracted 1000 persons from a general audience.

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