Over the weekend, Nature Medicine described… promising results [from] a somewhat different approach to ensuring that the virus leads to the death of cancer cells: if the virus doesn’t kill the cells directly, it revs up the immune system to attack them.
…The basic idea is to leverage decades of work on some common viruses. This research has identified a variety of mutations [that keep] viruses from growing in normal cells. It means that if you inject the virus into a healthy individual, it won’t be able to infect any of their cells.
But cancer cells are different, as they carry a series of mutations of their own. In some cases, these mutations compensate for the problems in the virus. To give one example, the p53 protein normally induces aberrant cells to undergo an orderly death called apoptosis. It also helps shut down the growth of viruses in a cell, which is why some viruses encode a protein that inhibits p53. Cancer cells tend to damage or eliminate their copies of p53 so that it doesn’t cause them to undergo apoptosis.
So imagine a virus with its p53 inhibitor deleted. It can’t grow in normal cells since they have p53 around, but it can grow in cancer cells, which have eliminated their p53. The net result should be a cancer-killing virus.
…In the new trial, the virus in question takes a similar approach. The virus, vaccinia (a relative of smallpox used for vaccines), carries a gene that is essential for it to make copies of itself. Researchers have engineered a version without that gene, ensuring it can’t grow in normal cells (which have their equivalent of the gene shut down). Cancer cells need to reactivate the gene, meaning they present a hospitable environment for the mutant virus.
The researchers added another trick by inserting a gene for a molecule that helps recruit immune cells (granulocyte-macrophage colony-stimulating factor, or GM-CSF)… By adding GM-CSF, the virus should help bring immune cells to the site of the cancer and activate them, creating a more aggressive immune response to any cells that survive viral infection.