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Dr. Michael Behr
Helmholtz Group Oncolytic Adenoviruses, DKFZ (German Cancer Research Center)
Im Neuenheimer Feld 242
+49 (0)6221 42-4451
“Armed” oncolytic adenoviruses for combined viro-/chemotherapy
In regard of the limited therapeutic efficiency of first generation oncolytic Ads on the one side and dose dependent side effects in chemotherapy on the other side, we develop Ads that combine the advantages of both strategies to overcome current obstacles of singular therapies. An ideal armed oncolytic adenovirus should exclusively infect and destroy tumor-cells with high specificity. The first attribute to this end is the modification of the adenoviral tropism via ablating the natural receptor interactions (de-targeting) and the introduction of tumor-specific ligands (re-targeting). The second aspect is molecular chemotherapy. We defined different positions in the adenovirus genome allowing the introduction of genes encoding prodrug-activating enzymes, like P450-derivates or Cytosine-deaminase, resulting in higher drug concentrations in the tumor after prodrug application. From such armed oncolytic adenoviruses we expect viruses that eliminates tumors by viral oncolysis and viral spread in the tumor tissue associated with a high drug concentration resulting from prodrug activation and mediated by strong bystander effects.