New immunotherapy for glioblastoma

A novel form of treatment that encourages the body's own immune system to recognize and eliminate cancer cells in the brain has achieved success, according to research done in test animals.

Advanced cancer is far more difficult to treat than cancer in its early stages. Treatment of brain tumors is particularly challenging because regulatory T-cells accumulate in brain tumors and suppress an immune attack.

Notably, a research team led by Burkhard Becher, PhD, of the Institute of Experimental Immunology at the University of Zurich in Germany, has now succeeded in treating advanced glioblastoma, which is one of the most dangerous types of brain tumors.

Their first step was to stimulate the body's own immune system in such a way that the treatment recognized and then killed the brain tumor cells, including those in the advanced stages of the disease. The initial objective of their new study was to break through the tumor's protective shield.

“We wanted to establish whether we can actually elicit an immune response to a tumor growing within the brain,” explained Becher. To this end, the team used the immune messenger substance, interleukin-12 (IL-12). When IL-12 is produced in the tumor, immune cells are stimulated locally in such a manner that the tumor is attacked and rejected. Once this procedure had worked well in the early stages of the tumor in test animals, the researchers waited until the tumor was very large and the life expectancy of the untreated test animals was less than 3 weeks. At this late stage, they did get an immune response, but tumor rejection occurred in only 25%  of the animals.

The researchers were successful when they drew on a new development in skin cancer treatment. They combined intratumoral IL-12 treatment with the intravenous administration of a novel immunostimulating drug that suppresses the regulatory T-cells. The rejection of the tumor then worked in 80% of the test animals.

“I have rarely seen such convincing data in preclinical glioma treatment,” said neuro-oncologist Michael Weller, MD, director of the Clinic for Neurology at the University Hospital Zurich. He added, “That's why this development should be tested as soon as possible in clinical trials.”

In a joint trial, the team then tested the treatment in a further tumor model which mimics the clinical situation of the brain tumor patient even better. Once again they were successful.

The findings of this current research have been published in the Journal of Experimental Medicine (2013; doi:10.1084/jem.20130678). These promising results do not mean that the treatment can already be as effective in brain tumor patients. That question must be examined in the next phase, and the research team is now actively seeking commercial partners for that phase.

As Becher explained, “We are cautiously optimistic, but it's time that we adopted completely new strategies to really get to grips with this fatal tumor.”

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