Lab Location: Anna Spiegel Center of Translational Research, Level 5
Associated Clinical Department: General Surgery
Influenza A Viruses:
- Understanding of virus-host interactions
- Development of oncolytic viruses to combat solid tumors
- Development of viral vectors for innovative vaccine concepts
Using genetic engineering we have defined the function of the viral protein NS1 as an antagonist of PKR, a protein involved in the anti-viral type I interferon response. Based on the fact, that cancer cells have defects in these antiviral pathways we have developed influenza A viruses lacking the NS1 protein as prototypes for oncolytic virotherapy. We currently develop stable influenza A viral vectors, which are targeted to tumor tissue and which code for therapeutic transgenes. Expression of chimeric proteins should improve the tumor ablative potential of the virus by i) enhancing the stimulation of a cytotoxic immune response or by ii) enhancing apoptosis. This goal implies our continuous interest to determine how the virus stimulates the innate immune response and how to modulate it. Findings have implication for the therapeutic application of the virus but also for a better understanding of viral pathology.
Our expertise in viral engineering allowed us to take part in a European commission sponsored consortium developing a new type of influenza A virus vaccine tested in a clinical phase-I trial. Our advances in viral vector development now also provide a platform for further development of the virus as an antigenic vector.
Characterization of the cancer-host interaction:
We are further interested in the understanding and modulation of the cancer-host interactions, since oncolytic viruses are thought to act via re-programming the cancer-associated immunosuppression. In this respect we have analyzed the role of the macrophage system. We identified specific combinations of toll-like receptor stimulation, which counteract the monocyte-associated immunosuppressive factor IRAK-M.
Collaborating with the groups of Prof. Oehler (Surgery Dpt.), Dr. Mechteriakova, Prof. Jensen-Jarolim (Pathophysiology Dpt.) and Prof. Wrba, we currently investigate the immunological infiltrate in tumor tissue as well as serological parameters to predict the response to chemo- and immunotherapy in solid cancer.
Effect of antiviral drugs on cancer:
The telomeres at the end of chromosomes regulate cell senescence as they are progressively shortened until the cells undergo apoptosis. Cancer is associated with a dysregulation of telomere lengthening by an enzyme called telomerase which supports cell growth and survival. Since the telomerase has a reverse transcriptase activity, licensed antiviral drugs which function as reverse transcriptase inhibitors could potentially inhibit telomerase. We currently investigate the impact of these drugs on cancer cell survival to possibly identify a new application for those substances in cancer therapy.