The results of a major trial carried out in Germany published in the journal Nature. The immune system is “guided” towards targeting an altered protein only found in cancer cells.
For the first time, a vaccine targeting one of the most difficult forms of brain cancer to treat, namely diffuse glioma, has proven to be effective and safe.
If the results achieved - for now on 33 patients - by researchers at the Deutsches Krebsforschungszentrum and the University Hospitals of Heidelberg and Mannheim are confirmed in larger groups of patients, this could open up an important new avenue in the treatment of these forms of cancer. Cancers that are often difficult to remove completely with surgery and also have only a limited response to chemotherapy and radiotherapy.
The vaccine triggered a powerful immune response against cancer cells in 30 out of 33 patients (93% of them), as reported in the scientific journal Nature. After three years, 84% of the 33 patients were still alive, which is much higher than can be achieved with traditional therapies. Furthermore, in 63% of these patients there were no signs of disease progression, which rose to 82% for those who had responded more specifically and powerfully to the immunisation - another result that could not be achieved otherwise.
An unconventional choice
By opting for a classic vaccine (i.e. for a technique that had not worked with other forms of cancer in the past), the German researchers went against the flow in certain respects.
Cancer immunotherapy has in fact made great advances in recent years, but by focusing on other strategies. For example, by attempting to eliminate the brakes “constructed” by tumours to block the immune system (resulting in the creation of a category of successful drugs called checkpoint inhibitors), or by genetically engineering certain types of “policemen” of the body (CAR-T cells). The German researchers, on the other hand, chose the more traditional vaccine.
How does it work?
The oncologists discovered that cancer cells of more than 70% of patients with diffuse glioma have a particular genetic mutation. A DNA error that leads to the “wrong” production of an enzyme (a protein) called IDH1, which has a powerful stimulating effect on tumour growth.
This altered protein (not found in healthy tissue) became the ideal target for the vaccine. In other words, the researchers inserted a weakened version of this protein into the vaccine, so that the immune system could get used to recognising it and destroy the (cancer) cells that possess it.
Prize-winning experiment
The team of researchers, led by Michael Platten, Medical Director of the Department of Neurology at the University of Mannheim, had already developed an initial version of the vaccine several years ago, which was able to halt the growth of IDH1-mutated cancer cells in mice, and Platten was awarded the German Cancer Prize in 2019 for this discovery. Encouraged by these results, he then decided to test the vaccine on humans, and started "enrolling" 33 patients, selected from several different German hospitals. All had diffuse astrocytoma (one of the forms of glioma).
A large proportion of the patients who took part in the trial showed a “pseudo progression” of the glioma at first. In other words, a swelling of the tumour, caused by the large number of immune system cells stimulated by the vaccine. However, these very cells then allowed the cancer cells to be restrained and reduced. Analyses confirmed that the patients had a particularly high number of T helper immune cells in their blood, with receptors that responded specifically to the IDH1 protein. The oncologists were also able to demonstrate that the immune cells had reached the brain tumour tissue.
In the coming months, the researchers will use the IDH1 vaccine in combination with checkpoint inhibitors for a new study. "Checkpoint inhibitors act as an immune ‘boost’", explained Platten, “We believe there is a good chance that they can activate the immune cells against the gliomas to an even greater extent."
