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| Delivering advanced gene-editing tools directly to the tumor site can improve the body’s defense against glioblastoma Image Credit: Gemini |
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 tumor.
GB is a brain tumor 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 tumor cells to prevent tumors 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 tumor models.
The researchers used this approach to study and modify two important proteins involved in cancer's defense against the immune system, PD-L1 and CD47, within live tumor 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 tumor growth and increased the number of immune cells entering the tumor, 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 tumors, accelerating the creation of personalized 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: Funding from the Brain Tumor Charity and Wellcome Trust has been crucial to success of the early stage of the project.
Published in journal: Advanced Science
Title: CD47 Knock-Out Using CRISPR-Cas9 RNA Lipid Nanocarriers Results in Reduced Mesenchymal Glioblastoma Growth In Vivo
Authors: Nadia Rouatbi, Adam A. Walters, Alaa Zam, Yau Mun Lim, Alessia Marrocu, Revadee Liam-Or, Joanne E. Anstee, James N. Arnold, Julie Tzu-Wen Wang, Steven M. Pollard, and Khuloud T. Al-Jamal
Source/Credit: King’s College London
Reference Number: med020525_02
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