“It’s like a balloon,” says Van den Pol. “If you keep blowing air into it, it explodes. The carcass is still there, but it’s no longer a balloon. And these are basically dead cells, unable to divide anymore or survive as intact cells.”
It’s not yet clear why VSV is such an effective tumor killer, although Van den Pol has several theories. One possible explanation may involve a tumor’s weak vascular system. Vessels that supply blood to tumors tend to be leaky, allowing a virus traveling through the bloodstream to cross an otherwise impermeable barrier into the brain, directly into a tumor.
Van den Pol says that VSV may also target cancer cells because of inherent defects in a tumor’s immune system. Typically, in the presence of a virus, normal cells launch an immune response by producing interferon, proteins that prevent viral infection in healthy cells. Tumors lack such strong viral defenses, providing an easy target for viruses.
There are several considerations that the team will have to face before moving to clinical trials. In its tests, the team observed live scans of the virus over a few days before sacrificing the animals for closer study. It remains to be seen how the virus will act on the brain over a longer timescale.
Additionally, the researchers used immuno-compromised mice. While these mice are still able to produce interferon as a local cellular defense, they have a weakened systemic immune system–one that’s unable to produce B and T cells that would otherwise destroy viruses. Van den Pol explains that such a weakened system allowed the team to insert transplanted human tumors in mice without their being rejected. However, in order to test the virus as an effective therapy, the team will have to make sure that a normal immune system doesn’t stamp out the virus before it has a chance to act on tumors.
“What usually happens with most of these tests is, you have a nice animal model where the virus spreads through the tumor,” says Samuel Rabkin, associate virologist in the department of neurosurgery at Massachusetts General Hospital. “In more-realistic models, the host may have a response to the virus that limits the effect.”