A vaccine designed to prevent a type of brain cancer completed a Phase 1 human trial. Scientists report that the vaccine is safe and triggers a significant immune response that should slow down tumor progression.

The vaccine developed by researchers at the German Cancer Research Center is meant to prevent diffuse gliomas, an umbrella term for a variety of tumors of the central nervous system. They’re the most common brain tumors and are usually incurable.

About 70% of cases of low-grade gliomas are due to a single gene mutation affecting an enzyme called isocitrate dehydrogenase 1 (IDH1). This mutation leads to the formation of a novel protein structure, known as a neo-epitope, which can be recognized as foreign by the patient’s immune system.

So the researchers, led by Michael Platten, designed their vaccine over years of work to target these IDH1 mutated cells.

“Our idea was to support patients’ immune system and to use a vaccine as a targeted way of alerting it to the tumor-specific neo-epitope,” said Platten, who is Medical Director of the Department of Neurology of University Medicine Mannheim and Head of Division at the German Cancer Research Center (DKFZ).

A vaccine that primes the body against the mutated proteins would effectively tackle brain cancer as well — that was the thinking in theory, at least. Now, the team has reported the results of a Phase 1 clinical trial for their experimental vaccine, which evaluated the immune response in 30 patients newly diagnosed with a IDH1-mutated glioma. Previously, the peptide vaccine was tested on IDH1-mutated cells in mice, where it halted the growth of new cancer cells.

In 93% of the patients, the immune system showed a specific response to the vaccine peptide. Important to note is that the immune response happened regardless of their genetic background. No serious side effects were reported.

In most vaccinated patients, the researchers observed swelling of the tumor. This is actually a good thing, showing that the immune cells are doing their job by invading the cancer cells. Serum tests showed that these patients had a large number of T helper cells in their blood.

“We were also able to demonstrate that the activated mutation-specific immune cells had invaded the brain tumor tissue,” reported Theresa Bunse from DKFZ, who coordinated the immunological analyses for these studies.

The three-year survival rate after treatment was 84% in the fully vaccinated patients, and in 63% of patients tumor growth had not progressed within this period. However, the researchers stress that they cannot draw definite conclusions about the vaccine’s efficacy at this point. The purpose of this initial trial was first and foremost to assess safety, as well as immune response. Phase 2 clinical trials will include more patients alongside a control group, which will make it better designed to assess vaccine efficacy.

In the follow-up study, the researchers also plan on combining the IDH1 vaccine with checkpoint inhibitor immunotherapy, which acts as an immune system booster.

“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 tumor progression in these patients. We believe that the IDH1 vaccine offers the potential for developing a treatment that can suppress these tumors more effectively and on a long-term basis,” commented study co-director Wolfgang Wick, Medical Director of the Neurological Clinic of Heidelberg University Hospital and Head of Division at DKFZ.

The findings were reported in the journal Nature.