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Specific transfer of oncolytic adenoviruses via mesenchymal stem cells for elimination of pancreatic tumor stem cells


This project is carried out together with PD. Dr. D. Nettelbeck, of the German Cancer Research Center (DKFZ). As a therapy against pancreatic CSCs, oncolytic adenoviruses are used because they replicate predominantly in tumor cells. During the replication cycle of oncolytic adenoviruses, they lyse the tumor cells and the release new infectious viruses, which re-infect tumor cells with concomitant lysis. A great advantage of oncolytic adenoviruses is their excellent and in clinical studies proven safety profile. The laboratory of Nettelbeck has genetically engineered these viruses to particularly infect pancreatic cancer cells. To selectively transport these viruses to the tumor, we use mesenchymal stem cells from the bone marrow of patients as viruses taxi. Such cell carriers protect the therapeutic viruses from neutralizing antibodies against adenoviruses, which occur in many patients due to previous natural infections with influenca viruses, and thus enable a systemic application. The virus-infected mesenchymal stem cells migrate into the tumor microenvironment of pancreatic cancer and are resident in the tumor stroma. Because of the tumor-specific replication of oncolytic viruses, we expect an elimination of pancreatic CSCs through specific viral lysis. We verify the functionality especially in our laboratory-established models for CSCs.