In laboratory studies at Cincinnati Children’s Hospital Medical Center, researchers have successfully treated the most common malignant abdominal tumor of childhood: neuroblastoma tumors. Researchers successfully treated the tumor in mouse models by administering a treatment based on a weakened version of the herpes simplex virus.
The study appears in the current online issue of Pediatric Blood and Cancer, the journal of the American Society of Pediatric Hematology / Oncology.
Neuroblastomas are solid cancerous tumors that usually begin in the nerve tissues of the adrenal gland, but may also begin in the nerve tissues of the neck, chest or pelvis. These are solid cancerous tumors that are 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, or spread to other areas of the body.
Researchers tested two treatment protocols: the adenovirus, a virus often associated with the common cold, and a weakened version of herpes simplex virus, which is most commonly associated with cold sores. Only the herpes simplex virus proved to be effective in treating neuroblastoma tumors, said Timothy Cripe, MD, PhD, director of the Comprehensive Musculoskeletal Tumor Clinic and Translational Research Trials Office at Cincinnati Children’s and 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,” Dr. Cripe said.
While 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, he said.
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 the destruction of cells from within, or cell suicide.
“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,” Dr. Cripe said.
Dr. Cripe and colleagues initially considered gene therapies to treat neuroblastoma tumors, but gene therapy is limiting in that the gene must be delivered to every single tumor cell individually. In comparison, oncolytic viruses can replicate and spread and theoretically can efficiently reach more tumor cells.
Dr. 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,” Dr. Cripe said.
Existing treatments for neuroblastoma tumors include the 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,” Dr. Cripe said.
The study was exclusively conducted in isolated solid tumors rather than in neuroblastoma tumors that have metastasized, but Dr. Cripe 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,” he said. “It has been difficult so far to obtain enough funding to conduct such studies in children.”
This study was supported in part by the Cincinnati Children’s Division of Hematology / Oncology and with grants from the National Childhood Cancer Foundation, Tee Off Against Cancer, the Sara Zepernick Foundation, and the American Cancer Society.
The study’s co-authors include Mark A. Currier, Lisa C. Adams, Yonatan Y. Mahller, Betsy Di Pasquale and Margaret H. Collins, all of Cincinnati Children’s. First author Nehal Parikh, formerly of Cincinnati Children’s, is currently with the University of Connecticut Children’s Hospital.