New Peptide vaccine shows promise in treating aggressive brain tumors

Physicians and cancer researchers from Heidelberg and Mannheim have now treated adult patients with advanced midline gliomas, difficult-to-treat brain tumors, with a peptide vaccine for the first time. The vaccine mimicked a mutational change in a histone protein typical of this type of cancer. The vaccine proved to be safe and induced the desired immune responses directed against the brain tumor.

Diffuse midline gliomas are among the most aggressive brain tumors. In this type of cancer, mutations characteristically occur in the gene encoding histone H3 (H3K27M), a packaging protein of DNA. The mutation gives rise to a novel protein structure - a so-called neoepitope - that can be recognized as foreign by the patient's immune system.

The researchers synthetically reconstructed the section of the histone H3 protein with the characteristic mutation. Using this peptide, they were able to curb the growth of H3K27M-mutated tumors in a mouse model*. Encouraged by the results, the team decided to test the mutation-specific vaccine produced at the University of Tübingen in patients in a phase I-trial**, which is still ongoing.

No serious side effects were observed in any of the vaccinated patients. Five of the eight treated patients developed specific immune responses against the mutant protein, which were dominated by CD4 T-helper cells. In one of the patients who had shown a strong immune response, the tumor regressed completely and she remained tumor-free for 31 months.

The vaccine peptide, which is comparatively long at 27 amino acids, worked in patients with different HLA variants. HLA proteins are responsible for the presentation of the mutant peptide on the cell surface and differ from person to person depending on their genetic background. The researchers also observed that immune responses decreased over time, so repeated administration of the vaccine could support a sustained effect.

Reference: Niklas Grassl et al, A H3K27M-targeted vaccine in adults with diffuse midline glioma

Nature Medicine 2023, https://doi.org/10.1038/s41591-023-02555-6