A novel vaccination strategy against certain malignant brain tumours could fundamentally improve treatment for patients.

Researchers from the German Cancer Research Centre (DKFZ), Mannheim University Medical Centre, Heidelberg University Hospital, and numerous partner institutions* have published encouraging long-term results from a clinical trial involving a vaccine that activates the immune system against a common genetic mutation in these tumours.

Published in the journal, Nature Cancer.

Gliomas are usually incurable brain tumours that are difficult to remove completely through surgery.

Chemotherapy and radiation therapy are also only effective to a limited extent.

These tumours often share a key characteristic: in the majority of cases, the cancer cells carry a common genetic mutation.

An identical genetic error causes a specific amino acid to be substituted in the IDH1* enzyme.

This results in a novel protein structure—a so-called neoepitope.

What makes this special is that, on the one hand, the neoepitope drives tumour growth—and, at the same time, it is recognised as foreign by the patient’s immune system, making it an ideal target for immunotherapies.

The research team from Heidelberg/Mannheim and Tübingen has developed a peptide vaccine that specifically trains the immune system to recognise and fight tumour cells with this mutation.

This vaccine was tested for safety and efficacy in a Phase 1 clinical trial (NOA 16) involving 33 patients with newly diagnosed high-grade astrocytomas, the most common form of glioma.

The patients received the vaccine in addition to standard therapy consisting of surgery, radiation therapy, and chemotherapy.

Long-Term Survival Significantly Improved

The results after up to eight years of follow-up are remarkable: 66 percent of study participants were still alive after eight years, and in 42 percent of cases, the disease had not progressed during the observation period.

Among some patients whose tumours could be completely removed surgically, survival rates were even significantly higher.

By comparison: In earlier studies, the median survival time for more aggressive tumour types was often only about 2.5 to 5 years.

In the current study, this threshold was significantly exceeded in many patients.

First author Lukas Bunse, head of the Neuro-Oncology Section at Mannheim University Medical Centre and Scientist at the DKFZ, explains the key to the vaccine’s success: “The mutated IDH1 is an important tumour driver. The mutation appears early in tumour development and, crucially, remains stable even as the tumour cells evolve.”

The Immune System as the key to therapeutic success

A key finding of the study analysis is the link between the immune response and disease progression.

Patients whose immune systems responded particularly well to the vaccine had significantly better long-term prognoses.

The vaccine activates two key components of the immune system: T cells, which directly attack infected or malignant cells, and B cells, which produce antibodies against the tumour.

In particular, the long-lasting antibody response was associated with a favourable disease outcome.

The researchers also demonstrated that immune cells activated by the vaccine actually migrate into the tumour.

In tissue samples, specific T cells were found only in those study participants whose tumours were under control—but not in those with rapidly progressing disease.

This is considered an important indication that the therapy not only triggers an immune response in the blood but also acts directly within the tumour.

Booster shots could prolong the effect

Initial observations suggest that additional vaccine boosters can reinvigorate the immune response even years later—without causing additional side effects.

This could help stabilise the therapy’s success over the long term in the future.

“The Phase I clinical trial primarily examines safety and the immune response. Caution is warranted when drawing conclusions about efficacy, as the study lacks a control group. Nevertheless, the results provide strong evidence of clinical benefit,” says Lukas Bunse.

“Based on the data we’ve collected, we’re now planning further studies to conclusively demonstrate the vaccine’s efficacy.”

Compared to other immunotherapeutic approaches, the vaccine developed by the research team has decisive advantages: Instead of developing individual vaccines for each patient, this therapy targets a common, tumour-specific mutation found in many patients.

This means it could be used as a standardised immunotherapy for a larger group of patients.

The vaccine can be combined with other modern therapies, such as immune checkpoint inhibitors or IDH enzyme inhibitors, which could further improve its efficacy.

“We are demonstrating here for the first time that a targeted vaccination strategy against a tumour mutation could lead to long-term survival benefits in brain tumours. This opens up a promising new avenue for treating cancers that have been difficult to treat until now,” summarises Michael Platten, Director of the Department of Neurology at Mannheim University Medical Centre and Head of Department at the DKFZ.

“We are pleased that we can now test the efficacy of this promising therapeutic approach in a multicenter, randomised Phase 2 trial with funding from the National Centre for Tumour Diseases.”

Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)