CORDIS provides links to public deliverables and publications of HORIZON projects.
Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .
Exploitable results
Some autonomous parvoviruses display a remarkable antitumor activity in rodents. Yet, in several instances, parvoviruses are potent enough to prevent tumors from developing. This led us to consider the production of recombinant parvoviruses to efficiently express anticancer transgenes in tumor cells, the effect of which may reinforce the intrinsic parvoviral oncosuppressive capacity. Limitations to recombinant parvovirus production had first to be overcome in order to achieve vector titers that were high enough to allow further assessment in animal tumor models. Improvements were effected in the DNA helper constructs, procedure cells and size of the inserted transgene, allowing to obtain recombinant virus stocks that were virtually free of contaminating wild-virus and contained up to 5x10 exp7, transducing units per ml of crude cell extract. This represents a 10exp3-10exp4 fold increase in titer, compared with virus stocks reported so far. The formation of tumors from HeLa cell xenografts in nude mice was reduced by 90% upon infection with interleukin (IL) 2-expressing recombinant parvovirus H-1 virus at an input multiplicity as low as 1 transducing unit per cell. Tumors arising from HeLa cells infected with transgene-free vector or with wild-type H-1 virus were not rejected at this multiplicity. Due to the expression of cytokine transgene, Il-2/h-1 virus- infected tumor cells became highly infiltrated with natural killer (NK) cells whose cytocidal program was activated, whereas little NK activity was detected in wild-type virus or mock-treated tumors. Altogether, these data show that the IL-2/H1 recombinant vector for transducing and expressing the cytokine gene at levels high enough to elicit an antitumor response. These data point to the possible application of recombinant autonomous parvoviruses to the therapy of some human tumors.
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