Brain tumor patients may eventually have a new treatment option: low doses of a drug that encourages the immune system to fight the cancer, according to City of Hope researchers.
Behnam Badie, M.D., chief of the Division of Neurosurgery and director of the Brain Tumor Program, led laboratory research into treatment with a category of drugs known as CpG oligodeoxynucleotides. Study findings recently were published in Clinical Cancer Research.
|Photo of Behnam Badie (Photo ©2005 Philip Channing)|
CpG oligodeoxynucleotides are synthetic strands of DNA that can stimulate immune cells.
“Brain tumors can be difficult to treat due to their location in sensitive tissue and the protective blood-brain barrier, which can prevent many drugs from entering the brain to treat the cancer,” Badie said. “But immune cells already have access to the brain, and they have the task of cleaning up damaged cells.”
As a tumor develops, it avoids attack by masking itself from the immune system, the body’s natural defense against disease. The immunosuppressive microenvironment around the tumor prevents the immune system from identifying cancer cells, so the tumor cells go ignored.
Past research into CpG therapies have demonstrated that they can overcome brain tumors’ immunosuppressive microenvironment and stimulate immune cells to battle the cancer, shrinking or even killing off the tumor. But high doses of the drugs caused serious side effects.
“Recent European studies in humans administered CpG therapy in one large dose, which led to treatment-limiting side effects such as brain swelling,” said Badie. “We proposed the idea of breaking treatment into multiple low-dose injections to see if we could overcome the toxic side effects while still providing an effective immune response.”
The study examined the effects of two or four low-dose injections of CpG therapy in laboratory models with glioma, the most common type of brain cancer. The drug destroyed the tumor in 70 percent of the models. And the mice remained free of tumors, even when scientists reintroduced glioma cells.
“With multiple low-dose CpG treatment a possibility, we’re also investigating the potential for developing more targeted versions than what is currently available,” said Badie. “Since CpG receptors are inside cells, engineering a nanotube with attached CpG may increase its efficacy without increasing toxicity.”
Badie now is developing a human clinical trial of multiple low-dose CpG treatment.
Findings from the study were published in the July 1 edition of the journal. Darya Alizadeh, research associate in the Division of Neurosurgery, was lead author on the paper. The National Cancer Institute and James S. McDonnell Foundation supported the research.