Mouse experiments with herpes-virus-based therapy for neuroblastoma show great promise against non-metastatic disease and researchers will begin testing against metastatic disease models, according to an article published online ahead of print by Pediatric Blood and Cancer, the Journal of the American Society of Pediatric Hematology/Oncology.

Although most neuroblastomas begin in the adrenal gland, they also originate in the nerve tissues of the neck, chest, or pelvis. Neuroblastoma is diagnosed in approximately 650 children in the United States each year, and most of these children are diagnosed before age five. In 70 percent of these cases, the cancer will have metastasized.

Researchers tested two treatment protocols: adenovirus and a weakened version of herpes simplex virus. Only the herpes simplex virus proved to be effective in treating neuroblastoma tumors, said Timothy Cripe, MD, PhD, senior author of the new study.

"It was surprising that with only one injection, we could make a large tumor disappear. We were able to cure a majority of the mice with neuroblastoma with a single injection of the virus," Cripe said.

Although the herpes simplex virus has been tested against adult cancers, this is the first study that shows promise in using the same therapy in children with neuroblastoma tumors.

The field of oncolytic viruses is a growing area in identifying new therapies for treating cancer. In using viral-based therapies, the disease-causing agent in the virus was deactivated before the virus was injected into the tumor. The virus then kills the tumor cells, in part, by activating the mechanism that triggers apoptosis.
"We have begun to unravel the mechanisms of how the cells are killed, so now, we can hopefully improve upon this mechanism in subsequent studies," Cripe said.

Cripe indicated that viral-based therapies could hold implications for other childhood and adult cancers. "We have data that suggest certain sarcomas in children are sensitive to this therapy. In addition, other research has shown in animal models that certain adult cancers are responsive as well. Furthermore, some clinical trials for adult cancers have been launched," Cripe said.

Existing treatments for neuroblastoma include surgical removal of the tumor, chemotherapy and radiation. In cases where the cancer has metastasized, blood and marrow transplants are conducted.

"There is clearly a need for other kinds of therapies," Cripe said.
The study was exclusively conducted in isolated solid tumors rather than in neuroblastoma tumors that have metastasized, but the group is currently testing the concept in tumor models that have metastasized. "There are a couple of reports that indicate the herpes simplex virus is effective in treating metastatic disease in adult cancers, so we are hopeful it will be effective in treating children," Cripe said. "It has been difficult so far to obtain enough funding to conduct such studies in children."