In collaboration with a team of physicians and scientists from Heidelberg University Hospital, DKFZ and the Universities of Mainz, Tbingen and Hamburg, Platten and his co-workers have now made the first successful step toward a vaccine that specifically targets the mutation in the tumor.
The researchers constructed an artificial version of the segment of IDH1 with the characteristic mutation using individual amino acids. This version of the peptide, which consisted of 15 building blocks, exactly matched one of the presentation molecules on the surface of the tumor cells. This is essential, because immune cells only respond to a target that is presented on so-called "MHC molecules" on the cell surface. If there is no such matching presentation, the body will not amount an immune response.
To draw conclusions about the human immune system from the vaccination experiments, the researchers used mice whose cells were equipped with human MHC molecules. "After vaccinating the animals with the peptide, we were able to detect immune cells and antibodies that specifically recognized the altered IDH1 of tumor cells rather than the normal form of the enzyme in healthy cells," says Dr. Theresa Schumacher, first author of the study.
In the experimental animals, this specific immune response induced by the vaccination arrested the growth of cancer cells that exhibited the characteristic IDH1 mutation. As hoped, the vaccination did not disrupt the functioning of the normal IDH1 enzyme, which plays a role in the energy metabolism of all healthy cells in the body.
"In some patients with low-grade glioma we also found spontaneous immune responses against altered IDH1," Platten says. "This is a good sign; it suggests that vaccinations based on the peptide can in fact support the body's own immune system in fighting cancer cells." This gives a "vaccination therapy" good chances of success, ac
|Contact: Dr. Sibylle Kohlstädt|
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)