Fighting cancer with oncolytic viruses

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Abstract
Although gene therapy has huge potential for modern medicine, our enthusiasm for its powerful potential must not cloud our judgment about the dangers of using increasingly diverse, yet relatively untested, replicating viruses Gene therapy is currently being studied in both the laboratory and the clinic in relation to many conditions, including cancer, heart disease, and autoimmune diseases. A few thousand patients have received genes in more than a thousand different clinical trials—overwhelmingly patients with cancer (two thirds of the trials), with most receiving non-replicative retroviruses or adenovirus as the vectors for the delivery of the new genes.w1 The use of viral vectors has now expanded from relatively safe, non-replicating viruses to the use of viruses that replicate more selectively in cancer cells than in normal cells (oncolytic viruses).1 The benefit of using these viruses is that as they replicate, they lyse their host cells. Cancer cells are ideal hosts for many viruses because they have the antiviral interferon pathway inactivated or have mutated tumour suppressor genes2 3 that enable viral replication to proceed unhindered. Adenovirus3 4 and herpes simplex virus,5 specifically mutated to replicate faster in cancer cells, are the main replicating human pathogenic viruses used in the clinic.3 To date, more than 250 patients have been treated with ONYX-015, a replicating adenovirus. Before the Helsinki protocols were approved, only a handful of studies had used live viruses injected into solid tumours. Currently, laboratory (and some clinical) studies are using many different viruses (such as Newcastle disease virus, reovirus, poliovirus, vesicular stomatitis virus, measles,6 and vaccinia7), selected for their ability to actively replicate in cancer cells.8 9 Some of these viruses are pathogens in humans, some also …