Talk about "potentially" good news.
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Talk about "potentially" good news.
Cancer-killing Measles Mass Produced
Hunts down and destroys tumors while sparing healthy cells
2/3/2005 12:58 PM
A system for mass producing a modified measles virus has been developed that promises potent cancer killing with fewer side-effects.
The system consistently converts the measles virus into a killer that hunts down and destroys cancerous cells but not healthy ones.
While likely years away from human use, the modified virus has proven to kill two kinds of human cancer cells, ovarian cancer and lymphoma, implanted in mice.
"When I saw the data, I was completely stunned," says lead researcher Stephen Russell of the Mayo Clinic in Rochester, Minnesota. "It's the sort of thing that, having worked on targeting viruses for about 15 years, I just couldn't believe that we'd finally got what we'd been hunting all that time."
Viruses have long attracted attention as potential cancer killers because they're highly efficient at targeting and taking over cells.
The measles virus became of particular interest because it has been found to have natural anticancer activity.
"But we had a concern that the measles virus may be a little too promiscuous in its ability to infect both cancer cells and non-cancer cells, so we wanted to develop a method whereby we could retarget the virus to infect cancer cells only," says Russell. "And we succeeded."
The researchers created their cancer killer by reprogramming the measles virus to target cancer cells rather than their normal targets.
To mass-produce the viruses, they created a molecular tag that they attached to structures on the outside of the virus.
This allowed them to grow engineered measles viruses on a special substrate while conserving their viral components for targeting and destroying tumors.
"It's very clean, very clear targeting," says Russell. "Our results show that we've efficiently ablated (destroyed) the ability of the measles virus to interact with its two natural receptors. And they also show that we can take our pick as to what new receptor we target and send the virus after it."
The research is reported in the journal Nature Biotechnology (read abstract).
Major advance in using measles virus against cancer
Saturday, February 05, 2005
ROCHESTER, Minn. – Feb. 4, 2005 – An international team of researchers has developed a system for mass producing a modified measles virus that destroys cancer cells without harming healthy cells.
The team led by Dr. Stephen Russell of the Mayo Clinic, published its findings in the current issue of Nature Biotechnology. In their report, the researchers demonstrate in mice a modified measles virus that has been reprogrammed to attack diseased, rather than healthy cells. They also detail a system that consistently converts the measles virus into a therapeutic cancer cell killer and mass produces them.
"When I saw the data, I was completely stunned." Russell said in a news release. "It's the sort of thing that, having worked on targeting viruses for about 15 years, I just couldn't believe that we'd finally got what we'd been hunting all that time. It's very clean, very clear targeting."
The results show that the reprogrammed virus efficiently destroyed the ability of the measles virus to interact with its two natural receptors, or cell surface proteins that the virus normally uses to gain access to the cell nucleus. They also showed that they could retarget the virus to whatever receptor they wished. In this study they retargeted the virus to attack two kinds of human cancer cells, ovarian cancer and lymphoma.
Russell, who is director of Mayo Clinic's Molecular Medicine Program, cautions that clinical application of the technology is probably still years away from use as a human therapy, but the concept has at last been proven in mice with human cancer tumors — a key step toward gaining FDA approval for clinical trials in humans.
Natural viruses are cellular parasites. To reproduce more viruses, they need to bind to a partner on their target cell, fuse membranes to enter the target cell and then take over the cellular machinery to reproduce themselves. When they succeed in doing this, an infection occurs. Viruses are so good at taking over cells that researchers have long dreamed of exploiting the specific attraction viruses have to certain cells and using it as a homing device to seek and enter cancer cells.
The measles virus became the focus of this vision several years ago when the surprising finding was made that the measles strain used internationally for vaccinations has natural anticancer activity.
Using bioengineering techniques, Russell's team reprogrammed the measles virus to seek a cancer cell to bind to instead of its natural binding partner. Then they invented a "molecular tag" that they attached to structures on the outside of the cancer-seeking measles virus.
This tag is the key innovation of their work and central to the team's success. Mass production of a retargeted virus was not possible before this specific innovation of the molecular tag — and research in this area was at an impasse. The tag enables researchers to grow retargeted measles virus on special "universal substrate cells," which is a cell culture used to grow biological organisms. At the same time the viral component for targeting and destroying tumors is preserved.
The result is, "The virus goes where it's meant to go, and it destroys the tumors in a targeted way,'' says Russell.
In addition to Russell, the Mayo Clinic research team includes Drs. Takafumi Nakamura, Kah-Whye Peng, and Mary Harvey, Suzanne Greiner and Charles James. Dr. Ian A.J. Lorimer of the University of Ottawa, also contributed to the study. Funding was by The Mayo Clinic Foundation, the Harold W. Siebens Foundation, and the National Cancer Institute.
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