Astrocytomas and oligodendrogliomas are subtypes of a brain cancer called 'glioma'. These incurable brain tumors arise from glial cells, a type of support cell found in the central nervous system. "Low-grade gliomas", which grow comparatively slowly, spread in a diffuse manner across the brain and are very difficult to completely eliminate through surgery. In many cases, the effectiveness of treatments with chemotherapy and radiotherapy is very limited. Gliomas can develop into extremely aggressive glioblastomas.
Low-grade gliomas have a particular feature in common: more than 70% of the cases exhibit the same gene mutation in tumor cells. An identical "typo" in the DNA causes the exchange of a single, specific protein building block (amino acid) in an enzyme called isocitrate dehydrogenase 1 (IDH1). As a result, most cancer cells do not follow the original building plan for the protein; at the 132nd position in the molecule's sequence, they insert the amino acid histidine instead of arginine.
"This frequent and highly specific mutation immediately aroused our attention as immunologists: In the cancer cells, the exchange of amino acids lends the protein novel properties that can be recognized by the body's own immune cells," says Prof. Dr. Michael Platten, who heads the Clinical Cooperation Unit "Neuroimmunology and Brain Tumor Immunology" at the DKFZ; he also works as a senior consultant in the Department of Neurooncology of Heidelberg University Hospital.
No other type of tumor displays the same mutation with such frequency. The mutant protein can reliably be detected using a highly specific antibody developed by Prof. Dr. Andreas von Deimling, a neuropathologist at the University Hospital and the DKFZ. This form of IDH1 is present on the surface of all tumor cells and is completely specific to the tumor. "This suggested that we might be able to use a vaccine to alert the patient's immune system to mutant IDH1, fighting the tumor
|Contact: Dr. Sibylle Kohlstädt|
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)