Brain tumors are sneaky. They hide in one of the most difficult places for drugs to reach. And they shield themselves from the body’s internal immune defenses, which otherwise would make short work of them.
But brain tumor patients may eventually have a new treatment option: low doses of a drug that encourages the immune system to fight the cancer.
|Behnam Badie (Photo ©2005 Philip Channing)|
“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,” said Behnam Badie, M.D., chief of the Division of Neurosurgery and director of the Brain Tumor Program. “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 unique environment around the tumor prevents the immune system from identifying cancer cells, so they go ignored.
Badie hopes to counter this with a category of drugs known as CpG oligodeoxynucleotides — synthetic strands of DNA that can spur immune cells into action.
Past research into CpG therapies have shown they can overcome brain tumors’ ability to knock down an immune response. This reinvigorates immune cells to battle the cancer, shrinking or even killing off the tumor.
On the down side, however, 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.
So his team tried breaking treatment into several low-dose injections to see if they could reduce the toxic side effects while still boosting 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 kept it away, 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.”
Nanotubes are tiny synthetic cylinders of carbon atoms that are a mere fraction the width of a human hair. They can be designed to carry CpG pieces directly to tumors. Early lab results testing CpG delivery with nanotubes suggests they are effective.
Badie and his team now are developing a human clinical trial of multiple low-dose CpG treatments. They hope to follow that with a nanotube study in the near future.