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Parvoviruses may be effective as cancer gene therapy vectors

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Replicating parvoviruses can be used to target colon cancer cells and may prove useful for cancer gene therapy, according to a report in the June Journal of Virology.

Several RNA viruses have been proposed as gene therapy vectors, the authors explain, but progress has been limited by the difficulty in designing tumor specificity into the viruses.Dr. Richard Iggo from Swiss Institute for Experimental Cancer Research in Epalinges, Switzerland and associates inserted binding sites for Tcf transcription factors into the P4 promoter site that controls the expression of NS1 and NS2 proteins of minute virus of mice (MVM) parvovirus. This modification makes the promoter responsive to wnt signaling, which is activated in colon tumors.Insertion of Tcf increased the selective inducibility of the promoters by 9- to 19-fold in different assays, the authors report, demonstrating that this modification of the parvovirus P4 promoter confers responsiveness to activation of the wnt signaling pathway.Parvovirus production increased 300-fold in the presence of wnt signaling by colon cancer cells in culture, the report indicates, but viral production was substantially less in other cell lines lacking expression of wnt signaling pathways.Toxicity of the virus also varied considerably in different cell lines, the researchers note, again showing selectivity for those cell lines with activation of the wnt pathway.Unfortunately, the investigators write, the burst sizes of virus were very low in cancer cell lines “and clearly incompatible with the therapeutic goal of disseminating new viruses within a tumor.””Overall, parvoviruses are extremely dependent on cellular functions to replicate their DNA,” Dr. Iggo told Reuters Health. “This explains why parvoviruses only replicate in dividing cells, which severely limits the number of sites in the adult body in which the viruses can replicate.””Parvoviruses are thus already considered to be very safe tumor targeting viruses,” Dr. Iggo said. “We go one step better than this by adding an additional layer of safety, namely to restrict the virus also to cells with activated wnt signaling.””The understanding we now have of the causal oncogenic defects in colon cancer is good enough that we can make viruses that target exactly the defect,” Dr. Iggo concluded. “It remains to be seen whether parvoviruses will have any advantages over adenoviruses for this type of work. We are certainly much further away from using parvoviruses than adenoviruses for clinical studies.”(Source: J Virol 2003;77:6683-6691: Will Boggs, MD: Reuters Health: July 4, 2003: Oncolink)


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Dates

Posted On: 7 July, 2003
Modified On: 3 December, 2013

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