Researchers and doctors from several centres across Germany, including the German Cancer Research Center, and the National Center for Tumor Diseases (NCT), carried out the first clinical trial to test a new vaccine against malignant brain tumours, according to a study published in the journal Nature (1). The results were very promising. Not only the vaccine was safe for all patients, but it also started the desired immune response in the cancerous tissue.
Vaccines against cancer are not a new idea. Typically, we get vaccines to avoid catching diseases, but it’s a slightly different method with cancer vaccines. These vaccines are designed to recognise specific proteins produced by cancer cells and are only administered when patients already have the condition. The idea is that these vaccines help the immune system to recognise and attack those particular cells, but not the rest of the body.
Cancer vaccines have been tested in various cancers, including a type of brain tumour known as diffuse gliomas. These usually incurable tumours are challenging to remove surgically, and treatments with chemotherapy or radiotherapy often show limited effect.
In more than 70% of patients, these tumours share the same genetic mutation, causing an identical error in a protein called Isocitrate dehydrogenase 1, or IDH1 for short. For the researchers, this is a perfect mutation to be used in a cancer vaccine to boost the immune system: It’s highly specific to gliomas and does not occur in healthy tissue. “Our idea was to support patients’ immune system,” explained Michael Platten, Medical Director of the Department of Neurology of University Medicine Mannheim. “A vaccine against the mutated protein allows us to tackle the problem at the root”.
For Platten and his team, this work started a few years ago when they created the first version of the IDH1 cancer vaccine, and successfully managed to stop the growth of cancer cells in mice (2). Encouraged by the positive results from their work in the lab, the team decided it was time to move forward to a phase I clinical study to test the vaccine in patients newly diagnosed with a glioma with an IDH1 mutation. Typically, phase I trials are designed to ensure the new treatment doesn’t have any major safety issues and obtain preliminary evidence that it could actually offer some therapeutic value.
A total of 32 patients across Germany were enrolled in the study and received 294 vaccines as well as the standard treatment for their cancer. Each patient received between four and eight vaccines. There were no signs of severe side effects amongst the patients, and over 90% showed the expected immune response to the vaccine. The team often found enlarged tumours, but this was caused by invading immune cells targeting cancer cells. “We were able to demonstrate that the activated mutation-specific immune cells had invaded the brain tumour tissue,” reported Theresa Bunse from the German Cancer Research Center. These patients had a particularly high number of immune cells that responded specifically to the vaccine”.
What’s more, preliminary results show that the vaccine was an effective way to treat these cancers. Over 80% of treated patients survived for more than three years after diagnosis, with 2/3 actually showing no progression within this period.
“Gliomas are diagnosed in around 5,000 people in Germany every year, of which about 1,200 are diffuse gliomas with an IDH1 mutation. Up to now, we have usually had only limited success in halting tumour progression in these patients”, explained Wolfgang Wick, Medical Director of the Neurological Clinic of Heidelberg University Hospital. “We believe that the IDH1 vaccine offers the potential for developing a treatment that can suppress these tumours more effectively and on a long-term basis.”
These results seem promising, but there’s still a long way to go until doctors can use this vaccine on a large scale. The following steps involve combining the cancer vaccine with immunotherapy to further boost the immune system and then a phase II clinical trial to determine whether the IDH1 vaccine leads to better treatment results than the standard treatment alone.
(1) Platten, M., Bunse, L., Wick, A. et al.A vaccine targeting mutant IDH1 in newly diagnosed glioma. Nature (2021). https://doi.org/10.1038/s41586-021-03363-z
(2) Schumacher, T., Bunse, L., Pusch, S. et al.A vaccine targeting mutant IDH1 induces antitumour immunity. Nature 512, 324–327 (2014). https://doi.org/10.1038/nature13387