Injecting natural signalling molecules help immune system shrink brain cancer tumour
Naturally-occurring signalling molecules injected directly into tumours can aid the body’s own immune response to destroy tumours in mice, researchers have found. The injection was combined with an existing chemotherapy to shrink tumours and increase survival.
Glioblastomas are the most aggressive form of brain cancer. With very limited treatment options, fewer than 30% of patients in England survive longer than a year after diagnosis. The tumours are fast growing and difficult to operate on because of their location in the brain. They are also extremely good at evading the immune system by attracting high numbers of regulatory T-cells, which inhibit the killer T-cells of the immune system. But it was this strategy that Professor Burkhard Becher at the University of Zurich, Switzerland, hoped to turn against the cancer.
Professor Becher knew that the regulatory T-cells create a protective environment around tumours in patients. In fact, higher levels of these cells in tumour biopsies correlates with increased mortality. Testing a number of signalling molecules called cytokines his team discovered one, called IL-12, that led to the clearance of tumours in mice. Cytokines are produced by many different cell types and cause other cells to move towards or away from the source. In this case IL-12 repelled the regulatory T-cells.
When the team analysed the killer T-cells that were now able to infiltrate and attack the tumour they discovered that these cells were a particular type characterised by CTLA-4 receptors on the cell’s surface. They therefore decided to combine the IL-12 treatment with another already-licensed chemotherapy that blocks the CTLA-4 receptor and increases the activity of the killer T-cells. These treatments combined had a much greater anti-tumour effect than either individually when tested on mice that had advanced tumour growth.
These are early studies and only in one type of animal. But if further tests in larger animals show similar promising results IL-12 could be rapidly put into clinical trials, Professor Becher says.