Gene Therapy Trial Takes Aim at Deadly Brain Cancer
Jefferson is one of 40 centers studying whether or not a new treatment will be effective in fighting incurable brain cancers
Researchers at Jefferson Medical College of Thomas Jefferson University, Philadelphia, are hoping to find out if gene therapy will be safe and effective in treating glioblastoma, a form of brain cancer.
Jefferson is among some 40 centers worldwide participating in what is believed to be the first organized international gene therapy trial of any kind. The trial is designed to see if gene therapy can not only delay disease progression, but also provide patients with an improved quality of life.
Neurosurgeon David Andrews, M.D., associate professor of neurosurgery, and his colleagues have already treated three patients, and are hoping to recruit several more. Glioblastoma multiforme afflicts approximately 6,500 people a year in the United States, and is the most common and deadliest type of brain tumor. Most patients who receive standard treatment--surgery and radiation, and sometimes chemotherapy--live for only about a year.
This is the first time researchers are studying a new treatment for newly diagnosed glioblastomas. Earlier studies were on recurrent tumors, which proved resistant to long-term therapy. “Cancer is a genetic aberration,” says Dr. Andrews. “Gene therapy is the treatment of the future for cancer.”
The treatment involves inserting a gene derived from a herpes simplex virus into glioblastoma tumor cells. When introduced during brain surgery, the therapy incorporates the gene for an enzyme, thymidine kinase (TK), into the DNA of actively dividing tumor cells. Patients are subsequently given the anti-viral agent, ganciclovir. The combination of the enzyme and virus destroys cancer cells.
The treatment has tremendous appeal, Dr. Andrews notes. “Primary brain cancers are very resistant to treatment, even palliation,” he says. “Biological therapies have shown some promise. Theoretically, it is a strategy upon which we can build. Traditional therapies--surgery, chemotherapy, and radiation--are limited in effectiveness.” Current treatments are designed to reduce symptoms, rather than cure the disease.
In the laboratory, mouse cells are transfected with a genetically engineered mouse leukemia virus that includes the herpes simplex gene for thymidine kinase. This genetically engineered “composite” virus will infect nearby dividing cells, but has been rendered incapable of dividing itself.
During surgery, after the tumor is resected, surgeons inject mouse cells containing the virus into the brain cavity. The virus--actually a retrovirus--then infects only surrounding cancer cells. The TK gene is incorporated into the host cells’ DNA, where it is transcribed and translated, producing the TK enzyme. This process occurs over two weeks, after which the patient is given ganciclovir. The drug is activated by the TK enzyme by a process called phosphorylation. The activated drug then kills the host cancer cell by shutting down its ability to replicate its DNA.
It may take several months for researchers to see any effects from the treatment, Dr. Andrews says.
The glioblastoma gene therapy protocol was developed by Genetic Therapy, Inc., a wholly own subsidiary of Novartis Pharmaceuticals Ltd., East Hanover, N.J. Novartis supports Dr. Andrews’ work.
For physician referral information call 1-800-JEFF-NOW or click here.