Experimental viro-and genetherapy of malignant glioma

The development of oncolytic adenovirus for glioma virotherapy is another focus of interest. Viruses are known as inductors of disease. But not every virus induces sickness in man. For this, so called “oncolytic viruses” could be used to fight against cancer. These viruses identify and solely replicate in tumor cells. Non-neoplastic cells were infected, but the virus does not replicate. As a consequence of replication, the tumor cell is killed. In our studies we are testing an adenovirus (Ad-DELO) which exclusively replicates in chemoresistant tumor cells and in glioma stem cell like cells. As a side effect, infection of the cells with Ad-DELO leads to enhanced sensitivity towards chemotherapy. Armament of Ad-DELO with a shRNA against a DNA repair enzyme, MGMT, further sensitizes infected cells to chemotherapy. Treatment of glioma-stem cell bearing mice showed prolonged median survival of mice having a therapy with Ad-DELO. Experiments were done as a joint research project in cooperation with the University of Munich (Klinikum Rechts der Isar) the Institute for Pathology of the Charité in Berlin and XVir Therapeutics, Munich..

Supported by: Federal Ministry of Education and Research (Contact persons: Dr. U. Naumann, Tübingen; Prof. Dr. M. Weller, Zurich, Swiss)