A mutation may provide cancer resistance

Arm your head against the tumor

Gliomas are brain tumors that spread diffusely in the brain and can become malignant glioblastomas. Glioma is diagnosed in around half of all brain tumors. “Even in the early stages, the tumor cells begin to migrate and pervade the brain with a kind of network structure. It is therefore impossible to completely remove them by surgery or radiation, ”says Professor Michael Platten, medical director of the Neurological University Clinic Mannheim and head of the clinical cooperation unit for brain tumor immunology at the German Cancer Research Center, describing the difficult situation. “Glioblastoma cells quickly become resistant to all therapies available to date. Targeted therapeutics that are successful in other types of cancer also usually do not work here. "

Sooner or later, almost all patients will relapse. Surgery, radiation therapy and chemotherapy can then often be used again, but life expectancy is still comparatively low.

"The immune system has everything it needs to fight the tumor"

At the DKTK, Platten and colleagues recently developed a new therapeutic vaccine against gliomas. “The advantage of a vaccine is that the cells of the immune system basically have everything they need to cross the blood-brain barrier and specifically fight a tumor in the brain. Many other active ingredients first have to be actively transported across the blood-brain barrier. In addition, the tumor cells often become resistant to such agents, ”says Platten.

After initial promising results in mice, the clinical trial NOA-16 is now examining whether its vaccine can prevent gliomas from recurring after treatment. The team of scientists around Platten is concentrating on the enzyme isocitrate dehydrogenase 1 (IDH1), which is characteristic and tumor-specific, especially in the majority of low-grade gliomas: at position 132, the cancer cells incorporate another protein component instead of the amino acid provided in the original blueprint .

Characteristic defect in glioma cells

Platten explains why this highly specific mutation is such a good point of attack for immunologists: “Parts of the modified enzyme are presented on the surface of tumor cells and are therefore recognizable as foreign to the immune system. In gliomas, this mutation occurs with a frequency of 80 percent. In addition, the IDH1 mutation is a very early change in the course of tumor growth and is therefore present in all tumor cells. ”In mice with cells of the human immune system, the vaccine stopped the growth of cancer cells with the characteristic IDH1 mutation. The function of the normal IDH1 enzyme, on the other hand, which plays a role in the energy metabolism in all healthy cells of the body, was not impaired by the vaccination.

Getting the right responses out of the immune system

For glioma patients, all centers of the DKTK offer a comprehensive molecular examination to check whether the vaccine could help them. By January 2017, 33 people with gliomas had been vaccinated as part of the phase I study. After the vaccination, the researchers use blood tests and imaging tests to examine how the immune system reacted to the vaccine and whether any side effects occurred
are.

Platten is so far satisfied with the course of the study so far: "As expected, all patients tolerated the vaccine well, and we were able to observe significant immune reactions in most of them." To control how long the immune protection lasts and other questions, the researchers are currently clarifying in detailed analyzes.

First results from NOA-16, which will be available at the end of 2017, should arouse great interest in immunotherapeutic research worldwide. After the start of NOA-16, clinical studies with vaccines against the IDH1 mutation have now also started in China and the USA. Platten hopes to be able to treat patients in a more targeted manner soon in a follow-up study. “The results of the study will tell us which people respond particularly well to the vaccine. We will not develop a panacea for glioma, but individual sufferers could benefit significantly from it. "

The German Consortium for Translational Cancer Research

The German Consortium for Translational Cancer Research, or DKTK for short, is one of six German centers for health research funded by the Federal Ministry of Education and Research and the federal states. In the DKTK, researchers from more than 20 university and non-university institutions across Germany bundle their strengths in the fight against cancer. The German Cancer Research Center in Heidelberg is a core center with eight university partner locations in a consortium with some of the strongest cancer research and cancer therapy centers in Germany.


Contact Person:

Prof. Dr. Michael Platten
Medical Director / Chairman
Neurological Clinic / Department of Neurology
University Medicine Mannheim,
University of Heidelberg
Theodor-Kutzer-Ufer 1–3
68167 Mannheim
0621 383-2885
[email protected]

Press contact:
Dr. Alexandra Moosmann
Press and public relations
German Consortium for Translational Cancer Research (DKTK)
German Cancer Research Center (DKFZ)
Foundation under public law
In Neuenheimer Feld 280
69120 Heidelberg
06221 42-1662
[email protected]