Immunostimulating Drug Developed for Malignant Brain Tumors

Laboratory research has revealed that it is now comparatively easy to treat cancer in its early stages. However, it is far more difficult to effectively treat advanced cancer. Treatment of brain tumors is particularly troublesome because regulatory T-cells accumulate in brain tumors and suppress an immune attack. In several steps using a new approach and a unique drug, Swiss scientists has now succeeded in doing exactly this in the instance of glioblastoma, one of the most lethal brain tumors.

Dr. Burkhard Becher’s team from the Institute of Experimental Immunology at the University of Zurich (Switzerland) first activated the body’s own immune system in such a way that it recognized and then killed the brain tumor cells even in advanced stages of the disease.

The first objective of their new study was to disrupt 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 Dr. Becher. To achieve this, the scientists used the immune messenger material, interleukin-12. When interleukin-12 is produced in the tumor, immune cells are stimulated locally in such a way that the tumor is attacked and rejected.

Once this procedure had worked well in the early stages of the tumor, the researchers waited in the next stage until the tumor was very large and the life expectancy of the untreated test animals was less than three weeks. “We only began treatment when it was, in fact, already too late,” stated the first author of the study Dr. Johannes vom Berg. The success rate was low, Dr. Berg added. “We then injected biopharmaceutical Interleukin-12 into the large brain tumor. This did induce an immune response but only led to tumor rejection in one-quarter of the animals.”

The researchers combined intratumoral interleukin-12 treatment with the intravenous administration of a novel immunostimulating agent that suppresses the regulatory T-cells. The tumor rejection then worked in 80% of the lab animals. “I have rarely seen such convincing data in preclinical glioma treatment, said Dr. Michael Weller, a neuro-oncologist and 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 assessed the treatment in an additional tumor model that mimics the clinical environment of the brain tumor patient even better. Furthermore, they were again successful. These exciting findings do not mean that the treatment can already be as effective in brain tumor patients. This new research has to be analyzed in the next phase for which the investigators are now actively looking for commercial partners. Dr. Becher concluded, “We are cautiously optimistic but it’s time that we adopted completely new strategies to really get to grips with this fatal tumor.”

The study’s findings were published November 25, 2013, in the Journal of Experimental Medicine (JEM).

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Institute of Experimental Immunology at the University of Zurich