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A normal cell warned by interferon shuts a virus down; many cancer cells have broken that alarm to grow, and this paper showed a common animal virus exploits exactly that break.
Interferons bind cell-surface receptors and set off a signalling cascade that produces both an antiviral state and growth-inhibitory or apoptotic signals. Many cancers acquire mutations in that pathway, which frees them from interferon's growth control. Stojdl and colleagues in John Bell's laboratory argued that the same cells must therefore have given up their antiviral defence, and tested it with vesicular stomatitis virus, an enveloped negative-sense RNA virus that is exquisitely sensitive to interferon.
Vesicular stomatitis virus replicated in and killed a range of human tumour cell lines at interferon doses that completely protected normal human primary cultures. A single intratumoural injection reduced tumour burden in nude mice carrying human melanoma xenografts. This is the mechanistic argument the whole field uses in plain words: the virus is not clever, the cancer cell is defenceless.
This is the reason oncolytic virotherapy is a strategy rather than an accident. Cancer cells frequently disable the interferon response because it restrains their growth, and the same break leaves them unable to mount the antiviral response a healthy neighbour mounts. Everything later in the field, including the choice of which virus to use and which gene to delete, is an attempt to widen that gap.
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Shares John C. Bell, Oncolytic viruses.
Shares John C. Bell, Oncolytic viruses.