Doctors now use cancer-killing viruses to treat some patients with lethal, fast-growing brain tumors. Clinical trials show that these therapeutic viruses are safe but less effective than expected.
A new study led by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) shows that the reason for this is in part due to the patient's own immune system, which quickly works to eliminate the anticancer virus.
The findings, published in the journal Nature Medicine, show that the body responds to the anticancer virus as it does to an infection. Within hours, specialized immune cells called natural killer (NK) cells move in to eliminate the therapeutic virus in the brain.
The researchers discovered that the NK cells attack the viruses when they express specific molecules on their surface called NKp30 and NKp46. "These receptor molecules enable the NK cells to recognize and destroy the anticancer viruses before the viruses can destroy the tumor," says co-senior author Dr. Michael A. Caligiuri, director of Ohio State's Comprehensive Cancer Center and CEO of the James Cancer Hospital and Solove Research Institute, and a senior author of the study.
"When we blocked those receptors, the virus has more time to work, and mice with these brain tumors live longer. The next step is to block these molecules on NK cells in glioblastoma patients and see if we can improve their outcome," says Caligiuri, who is also the John L. Marakas Nationwide Insurance Enterprise Foundation Chair in Cancer Research. This study of cancer-cell-killing, or oncolytic, viruses is an example of the value of translational research, in which a problem observed during clinical trials is studied in the laboratory to devise a solution.
"In this case, clinical trials of oncolytic viruses proved safe for use in the brain, but we noticed substantial numbers of immune cells in brain tumors after treatment," says senior author and neurosurgeon Dr. E. Antonio Chiocca, who was professor and chair of neurological surgery while at Ohio State University.
"To understand this process, we went back to the laboratory and showed that NK cells rapidly infiltrate tumors in mice that have been treated with the therapeutic virus. These NK cells also signal other inflammatory cells to come in and destroy the cancer-killing virus in the tumor."
The study used an oncolytic herpes simplex virus, human glioblastoma tumor tissue and mouse models, one of which hosted both human glioblastoma cells and human NK cells. Key technical findings include:
"Once we identify the molecules on glioblastoma cells that these NK cell receptors bind with, we might be able to use them to identify patients who will be sensitive to this therapy," Caligiuri says.
Ohio State University Medical Center: http://medicalcenter.osu.edu/Pages/index.aspx
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Drinking a few cups of coffee a day may help people avoid clogged arteries - a known risk factor for heart disease - South Korean researchers believe.
Researchers in China produce a herd of genetically engineered cows that are better able to ward off bovine TB.
The first model of a zombie epidemic to use real US census data lets you choose where the plague begins and how fast it spreads
Revealing new details about the origins of AIDS, scientists said on Monday half the lineages of the main type of human immunodeficiency virus, HIV-1, originated in gorillas in Cameroon before infecting people, probably via bushmeat hunting.
Few doctors — and few patients — realize just how profoundly early abuse, neglect and other childhood traumas can damage an adult's physical health.
From Dr Strangelove and water fluoridisation to climate change, scientific method and facts are not always enough to win over the sceptics
On a blog post at PLOS, the tropical disease expert Peter Hotez and postdoctoral fellow Jennifer Herricks take a run through the data on the biggest killers of children around the world in 2013, part of a new dataset from Global Burden of Disease study published in the January Lancet.
Tory MP David Tredinnick seems to believe that astrology could inform and improve UK healthcare. This view is misguided and potentially dangerous
Resistance to vital antimalarial drugs called artemisinins has spread across Burma to the Indian border. If not contained, it could ultimately hit Africa hard
Clostridium difficile sickens nearly half a million Americans annually, killing about 29,000, say federal health officials. They warn hospitals and nursing homes to tighten hygiene protocols.