Viruses kill pancreatic tumors in preclinical model

March 20, 2012

(Medical Xpress) -- An intra-tumor injection of a virus prevented further growth of some pancreatic tumors and eradicated others in mouse models of pancreatic ductal adenocarcinoma. However, some tumors continued growing despite this treatment, proving resistant to the viruses. The research is published in the March Journal of Virology.

About 95 percent of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAs). PDA is considered to be one of the most lethal malignancies, resulting in a five year survival rate of only 8-20 percent.

In this study, the researchers, led by Valery Z. Grdzelishvili of the University of North Carolina, Charlotte, tested several species of virus against , most notably (VSV), a type of virus that is commonly used in the laboratory. Previous studies had demonstrated that some other viruses, including adenoviruses, herpesviruses, and reoviruses, could be used to kill pancreatic cancer cells in some animal models of pancreatic cancer.

VSV has several qualities which make it attractive as a potential oncolytic (cancer killing) agent. First, unlike some other viruses (including adenoviruses),VSV replication does not require the cancer cell to express a specific receptor in order to infect that cell, and therefore it can infect most any cancer cell. Second, replication occurs in the of host cells, which means that there is no risk that it will cause healthy host cells to become cancerous, says Grdzelishvili. Third, this virus's genome is easily manipulated, which would make it fairly practical to adjust levels of foreign to enhance the virus' specificity for particular cancers, and its ability to kill them. Fourth, unlike with some other viruses, humans have no preexisting immunity to VSV.

In the study, the cancer-killing potential of several VSV variants was tested against 13 clinically relevant cell lines of PDA, including both primary PDA tumors and PDA metastases to the liver and lymph nodes, all derived from human patients, and compared these to adenoviruses, Sendai virus, and respiratory syncytial virus.

"In general, VSV variants showed superior oncolytic abilities compared to other viruses, and some cell lines that exhibited resistance to other viruses were successfully eradicated by VSV," says Grdzelishvili. "However, we found that PDA cells were surprisingly heterogeneous in their susceptibility to virus-induced oncolysis and several cell lines were resistant to all tested viruses." In producing and responding to interferon, many pancreatic cancers seemed to retain the normal antiviral responses that normal, healthy cells have towards viruses, he says.

Grdzelishvili emphasizes that the VSV's ability to kill cancer cells in mouse models by no means guarantees that it would perform similarly in cancer patients due to complex tumor microenvironments and compromised immune responses. Most animal models involve simply inserting human cancer cells underneath the animal's skin, so that the cancers and their environments are both quite different from cancer growing naturally in a human.

However, that are resistant to virus in laboratory dishes almost certainly would prove resistant in a human patient, which means that such virus-resistant cancers could be identified with simple laboratory tests prior to being applied to patients, says Grdzelishvili.

"Prescreening cells against an array of different viruses could identify the best option for treating a particular tumor," says Grdzelishvili. Combined virotherapy (analogous to combination drug therapy) could also potentially lead to enhanced cancer killing. "Understanding the mechanisms and identifying biomarkers of resistance is critical for the development of prescreening approaches and individualized oncolytic virotherapy against PDA," says Grdzelishvili.

Explore further: Virus attacks childhood cancers

More information: A.M. Murphy, D.M. Besmer, M. Moerdyk-Schauwecker, N. Moestl, D.A. Ornelles, P. Mukherjee, and V.Z. Grdzelishvili, 2012. Vesicular stomatitis virus as an oncolytic agent against pancreatic ductal adenocarcinoma. J. Virol. 86:3073-3087.

Related Stories

Virus attacks childhood cancers

August 29, 2011
Researchers from Yale University are looking to a virus from the same family as the rabies virus to fight a form of cancer primarily found in children and young adults. They report their findings in the September 2011 issue ...

Oncolytic viruses effectively target and kill pancreatic cancer stem cells

May 9, 2011
Oncolytic viruses quickly infect and kill cancer stem cells, which may provide a treatment for tumors that are resistant to conventional chemotherapy and radiation, particularly pancreatic cancer, according to new research ...

Cell receptor could allow measles virus to target tumors

August 25, 2011
Canadian researchers have discovered that a tumor cell marker is a receptor for measles virus, suggesting the possible use of measles virus to help fight cancer. Their findings appear in the Open Access journal PLoS Pathogens ...

Recommended for you

Long-lasting blood vessel repair in animals via stem cells

October 23, 2017
Stem cell researchers at Emory University School of Medicine have made an advance toward having a long-lasting "repair caulk" for blood vessels. The research could form the basis of a treatment for peripheral artery disease, ...

Synthetic hydrogels deliver cells to repair intestinal injuries

October 23, 2017
By combining engineered polymeric materials known as hydrogels with complex intestinal tissue known as organoids - made from human pluripotent stem cells - researchers have taken an important step toward creating a new technology ...

Study reveals connection between microbiome and autoimmune disorders

October 23, 2017
Many people associate the word "bacteria" with something dirty and disgusting. Dr. Pere Santamaria disagrees. Called the microbiome, the bacteria in our bodies have all kinds of positive effects on our health, Santamaria ...

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.