Harnessing the power from within: Neoantigen immunopeptidomics for the development of immunotherapies for the treatment of diffuse intrinsic pontine glioma (DIPG)
Occurring in the brain stem, diffuse midline glioma (DMG) is responsible for half of all brain cancer deaths in children. The brain stem controls vital functions such as breathing and heart rate, plus the nerves and muscles required for sight, hearing, movement, swallowing and speech. Primarily affecting children and young adolescents (median age 7 years), the average survival is just 9 months post diagnosis. Radiotherapy (offered at diagnosis) provides transient benefits and is considered palliative. Tumour location precludes resection and chemotherapy approaches (historical and current) have not increased survival.
Progress in treating DMG faces two major barriers: the lack of DMG-specific biological knowledge, and how to circumvent the brain’s protective mechanism, the blood brain barrier (BBB). The BBB acts as a shield to stop toxins moving from the blood stream into the brain, including chemotherapies and other pharmacological treatments.
Recently, recurring gene mutations that drive DMG disease initiation and progression have been identified. The unique combinations of mutations identified suggest the tumour is able to continue to grow and survive despite specific, mutation-matched, pharmacological targeting. Therefore, to improve outcomes for children with DMG, we look to utilise the patient’s own immune system. To harness the power from within in the fight against DMG. We will identify molecules presented to the patient’s immune system as foreign (i.e. tumour-specific gene products) that can be used in the development of novel immunological therapies.