Blood-vessel blocker aids cancer-killing virus

Cancer-killing viruses are a promising therapy for incurable brain tumors, but their effectiveness has been limited in part because immune cells rapidly move in and eliminate them.

That immune response might be slowed, and the virus given more time to kill cancer cells, by blocking the growth of blood vessels in the tumor, new research here suggests.

The animal study indicates that pretreatment with an antiangiogenic agent – a drug that blocks blood-vessel growth – might improve the effectiveness of cancer-killing viruses.

The study, led by researchers at the Ohio State University Comprehensive Cancer Center, is published online in the Journal of the National Cancer Institute with an accompanying editorial.

“Our work suggest that antiangiogenic agents can reduce virus-induced inflammation in brain-tumor tissue and improve the antitumor efficacy of oncolytic virus therapy by lengthening the time it takes the immune system to clear the virus,” says principal investigator Balveen Kaur, assistant professor of neurological surgery.

“Much additional work is needed to validate these findings in other tumor models, but we hope that our findings will eventually be translated into clinical trials and one day help patients.”

Kaur and her colleagues set out to learn how a cancer-killing, or oncolytic, virus affected the blood vessels in a brain-tumor model.

Kazuhiko Kurozumi, a visiting research scholar from Japan in Kaur’s laboratory, first implanted rat glioma cells into the brains of several groups of rats. Seven days later, he injected a cancer-killing virus, called hrR3, into the growing tumors. This virus is a modified form of herpes simplex virus type 1 that reproduces and kills only tumor cells.

The virus caused the tumor blood vessels to become significantly more leaky compared with tumor blood vessels from control animals, and high numbers of white blood cells – immune cells – entered the tumor tissue.

The virus also triggered a twofold or greater change in the activity of 48 of 84 genes that are involved in inflammation and immune responses. Of those genes that were highly changed was the gene for interferon-gamma (IFNg), a substance important for coordinating immune responses to viral infections.

“Together, these findings indicate that the oncolytic virus triggered a local immune response in the tumor that would curtail its effectiveness,” Kaur says.

In other rats, the researchers injected into developing tumors an agent that blocks blood-vessel growth. Four days after that, they injected the virus into the tumors. The agent is called cRGD (cyclic peptide of arginine-glycine-aspartic).

Tumors in animals that received the agent had significantly fewer blood vessels than control animals (28 vs. 62 per area of tumor), and the vessels were significantly less leaky. Also, fewer immune cells were drawn to the tumor from the bloodstream.

Furthermore, the treated animals showed a more than twofold drop in the activity of 19 genes associated with inflammation, including the gene for IFNg.

Finally, animals pretreated with the blood-vessel-growth inhibitor lived an average of 21 days, while control animals that received only the virus lived 17 days.

“The agent increased survival by about 23 percent,” Kaur says, “which means a lot because these tumors are very aggressive.

Source: Ohio State University

Related stories:

Existing anti-obesity drugs may be effective against flu, hepatitis and HIV
Viruses dramatically increase cellular metabolism, and existing anti-obesity drugs may represent a new way to block these metabolic changes and inhibit viral infection, according to a study published today in the journal Nature Biotechnology.
New way to control protein activity could lead to cancer therapies
Investigators at the Stanford University School of Medicine have found a way to quickly and reversibly fine-tune the activity of individual proteins in cells and living mammals, providing a powerful new laboratory tool for identifying — more precisely than ever before — the functions of different proteins.
New approach to gene therapy may shrink brain tumors, prevent their spread
Massachusetts General Hospital (MGH) researchers are investigating a new approach to gene therapy for brain tumors – delivering a cancer-fighting gene to normal brain tissue around the tumor to keep it from spreading. An animal study published in the journal Molecular Therapy, the first to test the feasibility of such an approach, found that inducing mouse brain cells to secrete human interferon-beta suppressed and eliminated growth of human glioblastoma cells implanted nearby.
Research indicates new virus is culprit, not bystander, in deadly skin cancer
University of Pittsburgh scientists are uncovering more evidence that a virus they recently discovered is the cause of Merkel cell carcinoma, an aggressive and deadly form of skin cancer.
Viral 'magic bullet' targets cancer cells with help of new compound
Researchers at McGill University and the affiliated Lady Davis Research Institute of the Jewish General Hospital – along with colleagues at the University of Ottawa and the Ottawa Health Research Institute (OHRI)–report a significant breakthrough in the use of viruses to target and destroy cancer cells, a field known as oncolytic virotherapy. Their results were published in the September early edition of the Proceedings of the National Academy of Sciences (PNAS).
Pores open the door to death
(PhysOrg.com) -- Our body is almost constantly being threatened by pathogens and cancerous cells that appear out of the blue. But the body puts up a fight: specialized cells in the immune system smuggle small molecules (granzymes) into cancer cells and those body cells that have fallen prey to viruses. The molecules then trigger off the diseased cells' built-in suicide program. There are two possible ways in which the granzymes gain entry into the cells under attack.
Plants make vaccine for treating type of cancer
Plants could act as safe, speedy factories for growing antibodies for personalized treatments against a common form of cancer, according to new findings from the Stanford University School of Medicine. The findings came in the first human tests of an injectable vaccine grown in genetically engineered plants.
HIV conquers immune system faster than previously realized
New research into the earliest events occurring immediately upon infection with HIV-I shows that the virus deals a stunning blow to the immune system earlier than was previously understood. According to scientists at Duke University Medical Center, this suggests the window of opportunity for successful intervention may be only a matter of days – not weeks – after transmission, as researchers had previously believed.

News discussion:

Medicine & Health news