Many gliomas carry mutation in the isocitrate dehydrogenase type 1 gene (IDH1). According to a new study published in Nature, immunization of mice with anti-IDH1-peptide vaccine could aid the immune system to ward off glioma recurrence.

“The IDH1 point mutation occurs with a high frequency in grade II and grade III gliomas, and is already used as a specific diagnostic marker,” explains Michael Platten from the University Hospital Heidelberg, Germany. “The mutation occurs early during the tumour development, meaning that all the tumour cells carry the same IDH1 mutation. This makes it an attractive target for immunotherapy.”

Platten's research group discovered that some patients with IDH1-mutated gliomas had spontaneous peripheral T-cell responses against the mutated IDH1 region. Such immune responses were never found in patients who had gliomas with the wildtype IDH1 allele.

“The spontaneous immune responses, however, were not sufficient to prevent tumour recurrence,” tells Platten. “Gliomas can remain stable for several years, but in almost all cases, they will eventually recur—often in a more malignant form. Could we complement chemotherapy and radiotherapy by boosting the immune response against the mutated IDH1 to prevent tumour recurrence?”

To address this question, Platten and colleagues used a transgenic mouse line in which the MHC molecules were replaced with human MHC, and vaccinated the MHC-humanized mice with a peptide containing the mutated IDH1 region. The vaccinated mice developed an immune response against the mutated IDH1.

“Our next step was to assess whether the immune response created meaningful anti-tumour immunity,” Platten says. The investigators induced sarcomas in the MHC-humanized mice, and transduced the sarcomas with the IDH1 mutation. Anti-IDH1 peptide vaccine was able to stop the growth of the tumours carrying the IDH1-mutation.

No adverse effects were observed in the vaccinated mice, but the safety of the peptide vaccine needs to be carefully tested in humans. Platten says that a Phase I trial of the anti-IDH1 vaccine is already planned. “It is yet too early to say, whether the vaccine will work humans, but if shown effective, the technique might provide secondary prevention for anaplastic gliomas,” he concludes.