What are the typical cancer cell characteristics that our immune system is directed against? Using a new biochemical method, scientists from the Neurosurgery Department of the Heidelberg University Hospital and the German Cancer Research Centre (Deutsches Krebsforschungszentrum, DKFZ) are now able to answer this question for each individual patient. The method is expected to help identify new target structures for individualized tumour vaccines.
Scientists are developing ever more sophisticated methods to support our body's immune system in its fight against cancer. However, although people may have the same type of cancer, they have different repertoires of immune cells. Doctors are therefore taking an individualized approach to immune system therapy: Immune cells are taken from a patient and placed in a culture dish where they are activated against the cancer using the cells' "matching" tumour proteins known as antigens. They are then injected back into the patient to help the immune system fight the tumour cells more effectively.
In order to achieve this, doctors first need to know the exact protein characteristics of a tumour against which a patient's immune cells are directed. Working groups headed up by Christel Herold-Mende of the Neurosurgery Department of Heidelberg University (Medical Director: Prof. Andreas Unterberg) and Philipp Beckhove of the German Cancer Research Centre have now tested a new method to find this out. By combining two different chromatography methods, the researchers first fractionated the whole protein mixture from a tumour tissue sample into individual components. They subsequently studied the individual protein components in the culture dish to find out whether the components are able to activate immune cells taken from a patient's blood.
The new method enabled the Heidelberg scientists to identify several proteins in a malignant brain tumour which were not previously known to be tumour antigens and which may serve as targets of an immune response against cancer. Four out of ten other astrocytoma patients examined were also found to have immune cells directed against the newly discovered tumour antigens. For the scientists, this was an indication of the clinical relevance of their results.The investigators were surprised to find that two of the newly discovered antigens are produced not only by the brain tumour cells themselves but also by what is called tumour stroma – the medical term for the tissue that surrounds a tumour and closely interacts with the cancer cells. “We know that the cancer can generate the production of particular proteins in the stroma cells,” says Philipp Beckhove. “The tumour depends on its surroundings. If we hit the stroma, the cancer will perish along with it – this represents a whole new approach in cancer treatment.”
Literature:Philipp Beckhove, Rolf Warta, Britt Lemke, Diana Stoycheva, Frank Momburg, Martina Schnölzer, Uwe Warnken, Hubertus Schmitz-Winnenthal, Rezvan Ahmadi, Mariana Bucur, Simone Jünger, Thomas Schueler, Volker Lennerz, Thomas Woelfel, Andreas Unterberg und Christel Herold-Mende: Rapid T-cell based identification of tissue antigens by automated two-dimensional protein fractionation. Journal of Clinical Investigatios 2010, DOI:10.1172/JCI37646