Research successes

Using immune responses to combat cancer

Dr. Georg Gdynia from the University Hospital of Heidelberg has been working in the field of cancer medicine for many years and has now discovered a promising new approach to cancer therapy

 

Dr. Gdynia’s current research focuses on so-called natural killer cells capable of destroying tumour cells within a matter of minutes. This makes them particularly interesting for cancer research – hoping that the effect of natural mechanisms can be intensified through new immunotherapies.

Dr. Georg Gdynia and his team have discovered a protein in the natural killer cells which can be used as a new agent against tumours. Gdynia has identified the High Mobility Group Box 1 (HMGB1) protein readily available in the granula of killer cells as a highly effective, natural weapon against cancer. HMGB1 paralyses a mechanism of energy production that is generally used by tumour cells, but not by healthy body cells. The protein interrupts an important metabolic pathway which helps tumour cells to break down glucose and convert it into energy. The cell’s entire molecular process system collapses as a consequence. In order to test the effect on complete tumours, the working group produced large quantities of the HMGB1 protein by stimulating the natural killer cells obtained from healthy blood donors to release the protein. In the mice treated with HMGB1, the colorectal tumours shrank in size and sometimes even disappeared entirely. The research team moreover proved that the HMGB1 protein can also kill particularly aggressive anoxic tumour cells. These tumour cells are mostly only loosely connected to the blood supply and require hardly any oxygen to survive. Experts have known for some time that these tumour cells are able to form remote metastases and are resistant to radiotherapy and chemotherapy as well as to attacks by immune cells.

The NCT Tissue Bank supported the project by providing quality-assured tissue samples. The samples were selected and prepared according to the project requirements and underwent a project-specific pathological, anatomical evaluation by a qualified pathologist prior to use. The tissue bank’s involvement ensures that sufficient cancerous cells are available for the investigation of interesting target structures.

Diagnosis through “energetic fingerprinting”

Dr. Gdynia has achieved another milestone in diagnostics, namely the development of a clinically applicable test: so-called “energetic fingerprinting” (EnFin) means that it is now possible to determine the proportion of highly aggressive anoxic cells in a patient’s tumour. His test could provide a new form of companion diagnostics that will enable the far more targeted use of immunotherapy – particularly in patients for whom conventional chemotherapies have not proven effective.

Based on this innovative test, the EnFin spin-off was established at the Institute of Pathology at Heidelberg University Hospital as part of the EXIST Transfer of Research programme of the Federal Ministry of Economic Affairs and Energy (BMWi).

As the spin-off’s CEO, Dr. Georg Gdynia is involved in the development, manufacture and approval of oncology diagnostics. EnFin has developed the world’s first prognostic test that can predict the likelihood of metastases developing and the response to treatment of countless different types of cancer.

Scientific Publications

Gdynia G, Sauer SW, Kopitz J, Fuchs D, Duglova K, Ruppert T, Miller M, Pahl J, Cerwenka A, Enders M, Mairbäurl H, Kamiński MM, Penzel R, Zhang C, Fuller JC, Wade RC, Benner A, Chang-Claude J, Brenner H, Hoffmeister M, Zentgraf H, Schirmacher P, Roth W. The HMGB1 protein induces a metabolic type of tumour cell death by blocking aerobic respiration. Nat Commun. 2016 Mar 7;7:10764.

Adelheid Cerwenka, Jürgen Kopitz, Peter Schirmacher, Wilfried Roth, Georg Gdynia. HMGB1: the metabolic weapon in the arsenal of NK cells. Mol Cell Oncol. 2016 Apr 15;3(4)

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