Cancer and multiple sclerosis (MS) are very different diseases, but scientists are discovering that research into one could have impact on the other. In newly published research, scientists applied their understanding of the biology of MS to improve how immunotherapy is delivered in brain cancer.
Immune cells cross the protective brain barrier in multiple sclerosis
MS is a chronic disease where the immune system attacks the body’s own nervous system. To do this, immune cells must first cross a protective layer of cells surrounding the brain called the blood-brain barrier (BBB). Once past the BBB, the immune cells cause inflammation of the brain and spinal cord.
The BBB protects the brain from disease-causing bacteria, viruses and toxins that may be circulating in the blood. But researchers have found that in MS, immune cells have found a way to get around this protective layer using a complex biochemical chain reaction to cross the BBB.
On the other hand, in order for immunotherapy to be successful in brain cancer, immune cells need to cross the BBB, but they are not able to do so. Using knowledge about how immune cells cross the BBB in MS, a team of researchers looked at this same pathway in brain cancer and developed a new molecule that can guide immune cells through the BBB and attack brain cancer cells.
Cell protein moves homing molecule into brain cancer cells
By studying two different types of brain cancer, glioblastoma and medulloblastoma, the researchers discovered that 2 proteins abundant in MS are found at lower levels in brain cancer cells. These proteins shuttle immune cells across the BBB in MS so their scarcity in brain cancer cells may explain why immunotherapies cannot reach the brain.
However, the researchers also found that brain cancer cells had high levels of another cell surface protein called ALCAM, which captures immune cells from the blood and helps them cross the BBB. To compensate for the 2 missing transport proteins, the researchers tried increasing the activity of ALCAM to guide immune cells past the BBB to brain cancer cells.
They designed a molecule that could home in on and grab ALCAM. This engineered molecule was able to locate and move into brain cells using a similar pathway to what is found in MS.
While the engineered homing molecule did not attack the cancer cell by itself, the researchers found that they could also add it to an engineered immune cell that does attack cancer cells, known as a CAR T cell. By combining a brain-targeting guidance system with cancer-killing immune cells, the researchers created a new therapy that effectively eliminated tumour cells in the brain.
New delivery mechanism could improve immunotherapy’s success
Immunotherapy is a promising form of cancer treatment, but researchers have had trouble successfully using it in brain cancer. Immune cells that target and eliminate cancer cells are not able to cross the brain’s protective barrier to get to the tumour, limiting immunotherapy’s usefulness in brain cancer.
While there is still a lot of work to be done before this homing molecule will be used in the clinic to treat brain cancer, the research is an important step forward. If we see the same success using immunotherapy for brain cancer that we have for other types of cancer, it could have a significant impact on survival and quality of life.
Eileen Hoftyzer, BSc