A brain tumour vaccine, cholesterol, a repurposed anti-psychotic and Boris Johnson

3 min read

Promising results have been reported from a landmark Phase 1 human trial testing a novel vaccine designed to help a patient's immune system better target brain tumours. The data suggests the experimental vaccine is safe and stimulates a significant immune response that slows tumour progression. Diffuse gliomas often share a common feature – over 70 percent of low-grade gliomas have a single gene mutation affecting an enzyme called isocitrate dehydrogenase 1 (IDH1). This IDH1 mutation is unique to gliomas and leads to the creation of novel proteins called neo-epitopes. The aim of the vaccine is to help a patient’s immune system learn to target these IDH1 mutated cells. A larger Phase 2 trial is currently being planned.

Cholesterol is a critical component in the growth and spread of brain tumours and recent research has discovered how cholesterol becomes dysregulated in brain tumour cells and has shown that the gene responsible for it could be a target for future drugs. The research pinpoints a gene called YTHDF2 as a crucial link in a chain leading to the development and growth of GBM. It works through a process set in motion by another gene with a well-established reputation for driving cancer progression, EGFR. EGFR is frequently overactivated in GBM. Researchers found that EGFR drives the overexpression of TYHDF2, which then sustains increased cholesterol levels for the invasive growth and development of GBM cells. By targeting YTHDF2 expression using YTHDF2 small molecule inhibitors we can potentially control GBM growth and this could be a powerful target for drug development.

These results will be of particular interest to researchers at the Brain Tumour Research Centre at QMUL, who are investigating potential new targeted approaches for glioblastoma.

From Korea comes this update as a research team has discovered a clue for developing a new treatment that suppresses the invasion of surrounding normal tissues in malignant brain tumours. The team discovered receptor molecules, which make malignant brain tumours infiltrate the entire brain and make surgery and radiation treatment impossible, and a drug that regulates such a process. Specifically, the researchers discovered NgR1, a regulatory protein for tumour cells that move along the cranial nerve circuit in malignant brain tumours. They confirmed that pimozide regulates this protein expression and inhibits tumour invasion through experiments on patient-derived brain tumour cell lines and preclinical trials. They also found that pimozide, used clinically as an existing antipsychotic drug, increases NgR1 expression by antagonising ubiquitin-specific protease 1 (USP1) and inhibitor DNA binding 1 (ID1), an upregulation of NgR1.The team expects pimozide will control highly invasive brain tumours in patients who cannot receive surgery.

News from Australia that the Government is providing $2.6 million to researchers at the University of Melbourne to use the latest information technology to improve the lives of people who have survived a brain tumour. The three-year grant opportunity will allow researchers to develop and demonstrate the impact of an online survivorship platform to better connect patients – and their families and carers – with the health care teams providing treatment. If you are interested in what the Australian Government are up you might want to read about what Boris Johnson said about the #braintumourpetition in the House of Commons on Wednesday.

In other news from the antipodes Australian and New Zealand children diagnosed with High Grade Gliomas (HGG) will now have access to one of the most promising treatments available worldwide. The NICHE-HGG Trial (a randomised pilot trial of Neoadjuvant checkpoint Inhibition followed by Combination adjuvant checkpoint inhibition in children and young adults with recurrent or progressive High Grade Glioma) is the first study to examine if immunotherapy can help boost the immune response in children with HGG, and will provide preliminary data on changes in patient survival.

Some interesting comments in this piece about the Stealth Autoguide cranial robotic guidance platform which helps brain surgeons be as precise as possible as they’re drilling into a patient’s skull to biopsy a brain tumour. The claim is that the tool is roughly 10 times more precise than the average brain surgeon and that this precision helps keep the patient safe and reduces the chances a surgeon might miss a small and hard-to-reach tumour or lesion that’s deep in the brain.

Developing more precise surgical methods to locate and remove brain tumour tissue whilst protecting normal healthy tissue is a particular interest of our Research Centre at Imperial College.

Finally, two items aimed at the research community reading this;

If you are a brain tumour researcher, you could receive feedback on your research ideas by applying to attend NCRI's proposals guidance meeting on 27th May 2021. The aim of proposals guidance meetings is to help investigators develop ideas for studies into an application that can subsequently be submitted to a funding committee.

Abstract submission is open for the European Association of Neuro-Oncology’s (EANO)2021 virtual meeting

Related Reading:

If you found this story interesting or helpful, sign up to our weekly e-news and keep up to date with all the latest from Brain Tumour Research.

Back to Research & Campaigning News