Engineered Virus Destroys Advanced Brain Tumors
Extends survival of mice with late-stage cancer
Betterhumans Staff
Credit: CDC/Dr. Erskine Palmer
Helpful infection: An engineered strain of herpes simplex virus has extended the lifespan of mice with advanced brain tumors, holding promise for a disease that usually kills soon after diagnosis
A virus engineered to kill cancer can significantly increase survival of mice with advanced human brain tumors.
Infecting and reproducing only in malignant glioma cells, killing them while leaving normal tissue unharmed, the virus's ability to prolong the life of mice with advanced tumors is considered important because such tumors are often diagnosed late in humans.
"Unfortunately, the average survival time for these patients has not improved in more than 30 years," says E. Antonio Chiocca of The Ohio State University Medical Center.
Malignant gliomas progress quickly after diagnosis and are nearly always fatal, says Chiocca. Average survival following diagnosis is about a year.
People with malignant gliomas are usually treated using surgery, chemotherapy and radiation.
"There is a real need for new therapies," says Chiocca.
Restoring reproduction
Initially, Chiocca and colleagues engineered a herpes simplex virus that could infect only malignant glioma cells. But the original virus reproduced poorly and therefore had a weak ability to kill cancer.
"Instead of making 1,000 copies of itself, it might only make 10," says Chiocca.
So the researchers went back to the drawing board and restored a deleted gene called ICP34.5 to increase the reproduction rate.
However, they modified the gene so that it was only active in cells producing a protein called nestin, a protein that sets malignant glioma and some other cancers apart from normal cells.
In lab-grown malignant glioma cells, the virus replicated at high levels.
Then the researchers tested it in mice with implanted human gliomas.
Simulated diagnoses
In one set of experiments, the virus was given seven days after tumor implantation. Untreated mice lived for 21 days while eight of 10 mice treated with the virus survived 90 days.
To simulate the reality of human glioma diagnoses, which usually come late in the disease's development, the researchers also conducted an experiment in which they injected the virus into tumors 19 days after implantation.
In this experiment, two of 10 animals treated with the virus survived 24 days after implantation while all 10 mice treated with a control virus had died by day 21.
"The treatment extended the animals' lives by several days," Chiocca says. "If we could achieve a proportional increase in humans with malignant glioma, that would be a very significant advance."
Chiocca cautions, however, that the study is preliminary and the virus cannot yet be used in humans.
The study is reported in the journal Cancer Research (read abstract).
http://www.betterhumans.com
Betterhumans Staff
Credit: CDC/Dr. Erskine Palmer
Helpful infection: An engineered strain of herpes simplex virus has extended the lifespan of mice with advanced brain tumors, holding promise for a disease that usually kills soon after diagnosis
A virus engineered to kill cancer can significantly increase survival of mice with advanced human brain tumors.
Infecting and reproducing only in malignant glioma cells, killing them while leaving normal tissue unharmed, the virus's ability to prolong the life of mice with advanced tumors is considered important because such tumors are often diagnosed late in humans.
"Unfortunately, the average survival time for these patients has not improved in more than 30 years," says E. Antonio Chiocca of The Ohio State University Medical Center.
Malignant gliomas progress quickly after diagnosis and are nearly always fatal, says Chiocca. Average survival following diagnosis is about a year.
People with malignant gliomas are usually treated using surgery, chemotherapy and radiation.
"There is a real need for new therapies," says Chiocca.
Restoring reproduction
Initially, Chiocca and colleagues engineered a herpes simplex virus that could infect only malignant glioma cells. But the original virus reproduced poorly and therefore had a weak ability to kill cancer.
"Instead of making 1,000 copies of itself, it might only make 10," says Chiocca.
So the researchers went back to the drawing board and restored a deleted gene called ICP34.5 to increase the reproduction rate.
However, they modified the gene so that it was only active in cells producing a protein called nestin, a protein that sets malignant glioma and some other cancers apart from normal cells.
In lab-grown malignant glioma cells, the virus replicated at high levels.
Then the researchers tested it in mice with implanted human gliomas.
Simulated diagnoses
In one set of experiments, the virus was given seven days after tumor implantation. Untreated mice lived for 21 days while eight of 10 mice treated with the virus survived 90 days.
To simulate the reality of human glioma diagnoses, which usually come late in the disease's development, the researchers also conducted an experiment in which they injected the virus into tumors 19 days after implantation.
In this experiment, two of 10 animals treated with the virus survived 24 days after implantation while all 10 mice treated with a control virus had died by day 21.
"The treatment extended the animals' lives by several days," Chiocca says. "If we could achieve a proportional increase in humans with malignant glioma, that would be a very significant advance."
Chiocca cautions, however, that the study is preliminary and the virus cannot yet be used in humans.
The study is reported in the journal Cancer Research (read abstract).
http://www.betterhumans.com
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