Surgically implanted devices and targeting immune cells in glioblastoma

6 min read

Brain Tumour Research:

Brain Tumour Research is delighted to announce it is working in partnership with the Medical Research Council (MRC) to fund ground-breaking research at Cardiff University, Wales.  

A project award of £500,000 will see Dr Ben Newland at the School of Pharmacy and Pharmaceutical Sciences at Cardiff University, Wales, and colleagues from universities throughout the UK, working to develop an innovative surgically-implanted, drug-delivery system which represents a “paradigm shift” in treatment for glioblastoma (GBM) patients.

The grant is our first partnership with the MRC, and the charity's first major investment in Wales. It is part of a £2 million cash injection announced this week by Michelle Donelan, Secretary of State for Science, Innovation and Technology. Dr Newland's project and another focusing on brain tumours represent two of four grants awarded following an MRC sandpit event where academic experts got together to design innovative new projects to address cancers of unmet need. Read more here.

Research:

Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas. Patients with high grade gliomas, particularly glioblastoma, have poor overall survival and lack predictive biomarkers to guide therapeutic treatment. To overcome this, researchers have developed an intratumoural microdevice (IMD) that is implanted inside a patient’s tumour during surgery and delivers very small doses of up to 20 drugs directly into the tumour tissue. It stays in the tumour for two to three hours and is then removed, along with the treated tumour tissue. This is then sent to the lab to test for treatment response.  Published in Science Translational Medicine, the device was tested in six patients (NCT04135807) and found to be safe, and the tissue was usable for downstream analysis with implications to replicating responses to temozolomide.

Designer Peptide Targeting Protein-Protein Interaction Could Become Glioblastoma Treatment.  Researchers have discovered that two proteins, EAG2 and Kvβ2, are both highly expressed in glioblastoma cells and interact with healthy brain tissue. Published in Nature Cancer, their findings show that the EAG2-Kvβ2 interaction is necessary in order for neurons to communicate with glioblastoma cells, facilitating tumour growth, invasion, and chemoresistance. In preclinical models, the team’s designer peptide prevented the EAG2-Kvβ2 interaction from occurring, which slowed the growth of the cancer, preventing it from spreading to surrounding cells while also resulting in the death of glioblastoma cells across all glioblastoma subtypes.

Effective reprogramming of patient-derived M2-polarized glioblastoma-associated microglia/macrophages by treatment with GW2580. Targeting immunosuppressive and pro-tumour immune cells has great potential to improve patient outcomes.  Colony stimulating factor-1 receptor (CSF1R) has emerged as a promising target for reprograming anti-inflammatory immune cells (M2-like glioblastoma-associated macrophages - GAMs). However, treatment data on patient-derived, tumour-educated immune cells (GAMs) and their influence on the adaptive immunity are lacking. 

This comparative analysis of CSF1R-targeting drugs on patient-derived GAMs and human glioblastoma avatars identified GW2580 as the most powerful inhibitor with the ability to polarize immunosuppressive GAMs to a proinflammatory phenotype, supporting antitumor T cell responses while also exerting a direct antitumour effect. These data indicate that GW2580 could be an important pillar in future therapies for glioblastoma.

Opportunities:

Survey for Black UK academics on their experiences of UK research funding. The University of Bristol is asking Black and Black heritage UK academics currently employed by a UK university and working in the Natural Sciences, Medical Sciences, Engineering, Informatics, Mathematics, and/or Technology to complete a 15-minute survey on their experiences of the national research funding environment and in particular the lack of equitable access to funding. This vital research will contribute to evidence-based policies that drive forward the cause of overcoming racial injustice in academia; If you can, please share it widely within your networks and with those it aims to survey. The survey deadline is the 30th September.

Register today for the 28th Annual Meeting and Education Day of the Society for Neuro-Oncology: Vancouver, Canada - November 16 - 19, 2023.  The early bird rate will be available until Friday 15th September 2023, at 11.59pm CT. After that, prices will increase.

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