Scientists report first successful step towards a vaccine that targets the mutation in brain cancer

Scientists report first successful step towards a vaccine that targets the mutation in brain cancer -

astrocytomas and oligodendrogliomas are subtypes of brain cancer called "Glioma ". These incurable brain tumors arise from glial cells, a type of support cell in the central nervous system. "Low-grade gliomas," that grow relatively slowly, so diffuse spread throughout the brain and are very difficult to remove completely by surgery. In many cases, the effectiveness of treatment by chemotherapy and radiotherapy is very limited. gliomas can develop extremely aggressive glioblastoma

low-grade gliomas have a common feature :. Over 70% of the cases have the same gene mutation in tumor cells. the same "typo" in the DNA causes the exchange of one specific building block protein (amino acid) in an enzyme called isocitrate dehydrogenase 1 (IDH1) therefore, most cancer cells do not follow the original construction plan for the protein;. to the 132nd position in the sequence of the molecule, they insert amino acid histidine instead of arginine

"This frequent and highly specific mutation immediately aroused our attention to immunologists :. In cancer cells, the amino acid exchange Ready properties of new protein that can be recognized by the immune cells of the body itself, "says Prof. Dr. Michael Platten, who heads the Clinical Unit of cooperation "Neuroimmunology and Brain Tumor Immunology" at DKFZ; he also works as a senior consultant in neuro-oncology department at Heidelberg University Hospital.

No other tumor type appears the same mutation with such frequency. The mutant protein can surely be detected using a highly specific antibody developed by Prof. Dr. Andreas von Deimling, neuropathologist at the University Hospital and the DKFZ. This form of IDH1 is present on the surface of all tumor cells and it is quite specific to the tumor. "This suggests that we might be able to use a vaccine to alert the patient's immune system to IDH1 mutant, the fight against the tumor without damaging healthy cells," explained Platten.

In collaboration with a team of doctors and University Hospital of scientists from Heidelberg, DKFZ and the Universities of Mainz, T-Tübingen and Hamburg Platten and his colleagues have now made the first successful step towards a vaccine that specifically target the mutation in the tumor.

researchers built a synthetic version of IDH1 segment with the characteristic mutation using individual amino acids. This version of the peptide, which has 15 building blocks, exactly in correspondence of presenting molecules on the surface of tumor cells. This is essential because the immune cells respond only to a target that is presented in so-called "MHC molecules" on the cell surface. If there is no such statement of correspondence, the body is a response immune.

to draw conclusions about the human immune system from vaccination experiments, the researchers used mice whose cells were equipped with human MHC molecules. "After the vaccination of animals the peptide, we could detect immune cells and antibodies that specifically recognized the IDH1 altered tumor cells rather than normal form of the enzyme in healthy cells, "says Dr. Theresa Schumacher, first author of the study.

in laboratory animals, this specific immune response induced by vaccination stopped the growth of cancer cells which had the mutation IDH1 feature. As expected, the vaccination did not disrupt the operation of the normal IDH1 enzyme, which plays a role in energy metabolism of all the healthy cells in the body.

"In some patients with low-grade glioma, we also found Spontaneous immune responses against IDH1 changed," says Platten. "This is a good sign, it suggests that the peptide-based vaccines can indeed support the immune system of the body in the fight against cancer cells." This gives a "vaccine therapy" a good chance of success, according to the Heidelberg doctors. In a clinical trial is expected to begin next year, with the support of the German Consortium for Translational Cancer Research (DKTK), they plan to consider the safety of the vaccine against gliomas based on IDH1 mutant in human patients for the first time.

"most low-grade gliomas can not be completely removed by surgery and therefore often return , "said Professor Wolfgang Wick, medical Director of neuro-oncology department and head of the clinical cooperation Unit" neuro-oncology "at DKFZ. "Patients should benefit greatly from a vaccine that prevents this from happening."