UAB and Children's of Alabama are once again part of cutting-edge medicine with the development of a therapy to target chemotherapy and radiation resistant pediatric brain tumors with engineered viruses.
Despite medical and surgical advances, more than 12,000 children and adolescents are diagnosed annually with cancer and approximately 2,300 die from the disease each year. Gregory Friedman, MD, associate professor of pediatrics at UAB and a scientist in the Neuro-Oncology Program at the UAB Comprehensive Cancer Center, treats patients at the Alabama Center for Childhood Cancer and Blood Disorders at Children's of Alabama. He is part of a team that is developing viral therapy and immunotherapy using herpes simplex virus to treat the pediatric cancer.
"With viral therapy, we use herpes virus to target and kill cancer cells. The virus also acts as an immunotherapy by stimulating the immune system to attack the tumor," he says. "The virus killing the cells results in an immune response that kills the tumor as well."
The scientists are using the herpes virus because it has been thoroughly studied and researchers know exactly how it works and which genes are involved. "Unlike some other viruses, there is a drug we can use against the herpes if we ever need to do that," Friedman says.
Through years of research at UAB, scientists have determined that certain genes in the lab-engineered virus could be removed so that the virus could not infect a normal cell. "The regular virus can damage both normal cells and cancer cells, but by removing specific genes from the virus, it will no longer affect normal cells. However, it can replicate and kill chemotherapy and radiation-resistant cancer stem cells," Friedman says. "I think of these cells like a queen bee in a hive. The queen bee gives rise to worker bees, just like cancer stem cells give rise to other tumor cells. You can take out as many worker bees as you want, but if you don't take out the queen bee, the hive will regenerate."
Friedman and his colleagues have found that medulloblastoma and other high-grade pediatric brain tumors are highly sensitive to the herpes virus, which makes it an ideal cancer killer. A phase one trial includes patients with progressive or recurrent tumors. Adult studies also are under way at UAB, and 35 adults received the therapy with no specific toxicities related to the virus.
"If this treatment proves safe for children and adults, it may be moved to a more front-line therapy," Friedman says. "Children, especially, get a lot of toxicity from chemotherapy and radiation, which can be damaging to the developing brain of a child and cause long-term side effects like hearing loss and cognitive issues. If we can give patients this therapy and reduce the number of toxic treatments, that would be a big benefit to them."
Safety and tolerability of the treatment is the primary objective of the trial. "Part of that safety is follow-up visits where we will monitor for any effects from this type of therapy," Friedman says. "A secondary goal is to determine if it is beneficial to the patient, so we will explore for any tumor responses related to the therapy and for improvement in the child's quality of life."
Recent grant awards from the Rally Foundation for Childhood Cancer Research, St. Baldrick's Foundation, and the Department of Defense are providing support to Friedman and his colleagues as they continue to use viral therapy and immunotherapy to fight this invasive cancer. "Herpes tends to be a generalized killer of tumors, so we also plan down the road to have trials using the virus outside the brain in solid tumors," he says.
