"We are hoping to find ways to boost the immune system to help overcome these tumours", says Anna Dimberg, Associate Professor at the Department of Immunology, Genetics and Pathology.
Photograph: Knut och Alice Wallenbergs Stiftelse
Glioblastoma is a severe type of brain tumour that is currently incurable. Anna Dimberg and Magnus Essand are researching a method that activates the body's own immune system by building a "boot camp" in the brain where the immune system's T-cells are trained. A specially designed virus could also help fight the tumour.
Glioblastoma brain tumours are incredibly aggressive and there are no treatments that cure patients yet.
"Surgery, radiation, and chemotherapy are all used, but they are not enough as the tumours have spread through the brain already. That is why we are hoping to find ways to boost the immune system to help overcome these tumours", says Anna Dimberg, Associate Professor at the Department of Immunology, Genetics and Pathology.
However, activating the immune system in the brain is not easy, as the brain has a completely different immunology to the rest of the body. The so-called T-cells that can attack tumours have a hard time reaching the brain and the immunological reaction is not as effective here.
"The brain has to protect itself from major inflammation as swelling inside the brain is very dangerous. So the brain must be protected. There are few immune cells that can activate T-cells, and there is generally a lack of T-cells", says Magnus Essand, professor at the same department.
Activating the T-cells in the brain
But in this particular case, the T-cells can save lives, which is why the researchers are working to find ways to get a strong immune response inside the brain by activating the T-cells and helping them get into the tissue.
Normally, the activation of the immune system occurs in the lymph nodes, but in the brain the molecules from the tumour cells must be transported down to the lymph nodes in the neck region for there to be an immune reaction to the tumour.
"The immune system needs to learn to recognize the tumour and transportation to the lymph nodes is a fairly ineffective. What we want is to create a lymph node-like structure close to the tumour in the brain in order to incite an immune response on site", says Anna Dimberg.
Magnus Essand likens it to a field hospital or a boot camp for the immune system's T-cells that are at war with the tumour. The researchers are also using a specially designed virus as a targeting system to reach the brain.
"Viruses trigger powerful immune responses. We are working with two types of virus that both are able to find their way into the blood vessels inside the brain. With it the virus brings building blocks needed to begin construction of the field hospital or boot camp. Another advantage of these viruses is that they are able to infect tumour cells, enabling the immune system to better recognizes tumour cells."
"We also want to alter the blood vessels in the brain to make it easier for T-cells to enter the tumour.We are approaching this in a number of ways and have very promising results in our animal studies, so we really hope that this is something that will be of use in the future," says Anna Dimberg.
A long way from a finished treatment
However, there is a long way to go before this treatment reaches health care. Besides good results in their preclinical studies, researchers need to be sure that the treatment does not present unwanted side effects or long-term toxic effects. Magnus Essand has previously developed viruses that are currently used to treat cancer at Uppsala University Hospital, so he knows that there is a lot to do before research results reach patients.
"The whole process must be carefully documented before there can be an application with the Swedish Medical Products Agency, as well as the approval of an ethics committee. The Medical Products Agency has a large regulatory framework and their job is to examine patient safety and ask critical questions."
The researchers must now show that the treatment does not lead to inflammation and that the new structures do not remain in the brain after the tumour is gone, as that would mean that there is remaining hyperreactivity in the brain.
"Our government appropriations cover five years and somewhere at the end of that period we might have the data required to proceed to the Swedish Medical Products Agency. First, a significant amount of basic research is needed," says Anna Dimberg.
It has been found that the lymph node-like structures can develop in the vicinity of several different types of cancer, so there is great interest in the scientific community. But so far very little is known about exactly how they work and how the immunological activation occurs.
"There is a lot we need to find out on this journey, so it is very exciting even from a biological perspective. The hope, of course, is that it leads to something that can benefit patients," says Anna Dimberg.
Facts: Immunotherapy for brain tumors
The project "Breaking barriers to efficient immunotherapy of brain tumours" has received funding from the Knut and Alice Wallenberg Foundation, with SEK 31,500,000 disbursed over five years. The project began in January 2020 and is being lead by Associate Professor Anna Dimberg and professor Magnus Essand at the Department of Immunology, Genetics and Pathology, Uppsala University. Professor Bengt Westermark and professor Elisabetta Dejana at the same department are also involved with the project and contributing their important expertise in neuro-oncology and blood-brain barrier biology.
