King's College London

A new study led by Khuloud Al Jamal, Professor of Drug Delivery & Nanomedicine, has found an innovative strategy to combat glioblastoma (GB), a fast-growing and aggressive type of brain tumour.

GB is a brain tumour originating in the brain or spinal cord. Despite advances in cancer treatment, it can remain resistant to therapies, including immune checkpoint (ICP) blockade therapies. ICP blockade works by targeting specific proteins on immune or tumour cells to prevent tumours from evading the immune system. While effective in other cancers, this approach has shown limited success in treating GB. The is due to complex interactions between immune cells and glioblastoma stem cells (GSCs), which suppress the immune response and reduce the effectiveness of these therapies.

In the study, published in Advanced Science, Professor Al Jamal and her team revealed how they have taken a novel approach to overcome this challenge by focusing on the mesenchymal subtype of GSCs, which is particularly aggressive and therapy resistant. The study employed lipid nanoparticles (LNPs) — tiny, fat-based carriers — to transport CRISPR RNAs, an advanced gene-editing tool, to GSC and immune cells in therapeutically relevant tumour models. 

The researchers used this approach to study and modify two important proteins involved in cancer's defence against the immune system, PD-L1 and CD47, within live tumour models. They found that targeting CD47 was more effective than PD-L1 for a specific type of brain cancer called the mesenchymal subtype of GB. By editing the CD47 gene, they slowed tumour growth and increased the number of immune cells entering the tumour, making the cancer cells easier for the immune system to attack.  

In context of GB, future research will focus on larger-scale studies and long-term experiments to refine this approach. The goal is to use these methods on models developed from patient tumours, accelerating the creation of personalised therapies. These therapies will be tailored to both specific GB subtypes and the unique characteristics of individual patients. Professor Al Jamal’s work has the potential to significantly improve outcomes for one of the most difficult-to-treat cancers, bringing new hope to patients and their families.

The study benefited from an experimental mouse model developed by the team of Professor Steven Pollard, a group leader at the Centre for Regenerative Medicine and the Edinburgh Cancer Research UK Centre, and a cross-School collaboration with Professor James Arnold from the Comprehensive Cancer Centre, KCL. Funding from the Brain Tumour Charity and Wellcome Trust has been crucial to success of the early stage of the project.