A viral view: Researchers at Yale University have genetically engineered a virus (green) that specifically attacks brain tumors in mice (red). The virus kills the primary tumor masses (B) and migrating tumor cells (E), while leaving healthy tissue intact.
Van den Pol/Yale University

Biomedicine

A Viral Attack against Brain Tumors

A rabies-related virus seeks out and destroys tumors in the brain.

  • Monday, March 3, 2008
  • By Jennifer Chu

This year, more than 21,000 people will be diagnosed with some form of brain cancer, according to the National Cancer Institute. While benign forms are relatively easy to treat, malignant tumors require a combination of surgery, chemotherapy, and radiation. Even then, tumor cells may remain deeply lodged, replicating and spreading quickly through healthy brain tissue.

Now researchers at Yale University have found that a virus that's in the same family as rabies effectively kills an aggressive form of human brain cancer in mice. Using time-lapse laser imaging, the team watched vesicular stomatitis virus (VSV) rapidly home in on brain tumors, selectively killing cancerous cells in its path, while leaving healthy tissue intact. What's more, Anthony Van den Pol, lead researcher and professor of neurosurgery and neurobiology at Yale, says that VSV is able to self-replicate and produce secondary lines of defense.

"A metastasizing tumor is fairly mobile, and a surgeon's knife can't get out all of the cells," says Van den Pol. "A virus might be able to do that, because as a virus kills a tumor cell, it could also replicate, and you could end up with a therapy that's self-amplifying."

In the past few years, scientists have looked to viruses as potential allies in fighting cancer. Researchers at the Mayo Clinic are engineering the measles virus to combat multiple myeloma, a cancer of the bone marrow. And while various groups have seen limited results after injecting herpes and polio-related viruses directly into brain tumors in mice, Van den Pol wanted to find a more effective cancer-killing strain.

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His search for a virus candidate began six years ago, when he and his colleagues tested the effect of different viruses on brain tumors in culture. Repeatedly, VSV came out "at the top of the heap." The team grew the virus through many generations, isolating strains that infected cancer cells quickly while having a slow effect on healthy cells. The researchers recently ran the most effective strain through a number of tests in live mice, and they've published their results in a recent issue of the Journal of Neuroscience.

In its experiment, the team transplanted glioblastoma--the most common and aggressive form of human brain cancer--into the brains of mice. Prior to transplantation, researchers genetically engineered the tumor cells to express a red marker, which, once inside the brain, would show up in laser microscopy scans. Similarly, Van den Pol inserted a green marker in VSV cells and injected the virus intravenously through the tail. Within a few days, researchers observed that the green virus found its way to the brain and selectively infiltrated red tumor masses and individual tumor cells, while avoiding normal cells. Van den Pol says that as the virus infects tumors, cancerous cells start to turn green, swelling up until they eventually burst.

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hsfrey

13 Comments

  • 1444 Days Ago
  • 03/03/2008

Inflammation ?

The article neglected to mention the problem that killed the experimental (human) subjects in a recent immunological study targeting brain tumors in children. It was so effective, and the tumor cells died so fast, that a massive inflammatory response made the brain swell and killed the patients.
They probably didn't see that here since the mice were immunocompromised.

Reply

cowman11

1 Comment

  • 1441 Days Ago
  • 03/06/2008

Re: Inflammation ?

In the article it mentions... "The team grew the virus through many generations, isolating strains that infected cancer cells quickly while having a slow effect on healthy cells."  I wonder if through the same type of selection process the life span of the virus could be shortened dramatically.  Slowing the viruses ability to spread would also reduce the rate at which the tumor recedes and hopefully minimize inflammation.
Amazing article though!  Hope they can figure out a way to make it work.

Reply

odetoazam

1 Comment

  • 1444 Days Ago
  • 03/03/2008

i am legend

isn't this what i am legend was about.

Reply

enantiomer2000

66 Comments

  • 1444 Days Ago
  • 03/03/2008

Re: i am legend

the only difference is i am legend was an  (pretty entertaining) implausible science fiction movie, while this is reality. These treatments won't cause zombie legions to destroy new york city.  the inflammation question is the most valid.  if they can control that in humans i would say this sounds like a very good approach.  billions of little surgeon scalpals enacting programmed mutation seems a fitting fate for these rogue cells.

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lordewoks

1 Comment

  • 1444 Days Ago
  • 03/03/2008

Re: i am legend

Right, I'm sure all those scientists in I Am Legend thought that the idea of the engineered viruses mutating to create zombies was implausible as well.

Not that I'm saying the viruses will mutate, but in case they do, I would recommend following the Zombie Outbreak Protocol: http://zombie-protocol.blogspot.com/

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shomas

246 Comments

  • 1424 Days Ago
  • 03/23/2008

potential clinical trials

The article expressed concern over the effectiveness of a viral therapy in non-immuno-compromised subjects.

It might be possible to take advantage of that in a therapy ware the subject is given immuno-suppressing drugs in order to allow the virus to do its work on tumors then return the immune system to normal to kill off the virus. Immuno-suppressing drugs may even be used to modulate the rate of attack on tumor cells to minimize inflammation.

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bgordski

5 Comments

  • 1357 Days Ago
  • 05/29/2008

Re: potential clinical trials

Please remember that both radiotherapy and chemotherapy compromise the immune system. This usually works against a patients' survival especially if vaccines are used. Ironic to see a positive use for immunosupression.

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shomas

246 Comments

  • 1250 Days Ago
  • 09/13/2008

Re: potential clinical trials

Good point. Considering a brain tumor patient may not have many options, some doctors may feel their patient might be a good candidate for this treatment, assuming it accepted by the medical community for treatment.

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