Targeting Paediatric Diffuse Midline Glioma Using Cell Therapy

Jun 12
4 min read

Updated: Jun 13

A further grant has been made to Dr Ashley Vardon, NIHR Academic Clinical Lecturer, Institute of Cancer and Genomic sciences, University of Birmingham.

DIPG Neurospheres - Image: University of Birmingham

Recently, CAR T-cell therapy has emerged as a treatment option for diffuse midline glioma (DMG) including diffuse intrinsic pontine glioma (DIPG). After treatment some patients with H3 K27M-mutated DMG benefited from clinical and neurological improvements, and reduced tumour size. However, these tumours have a high risk of relapse even after successful treatment due to the presence of senescent cells. These cells are created by the standard-of-care radiotherapy and although they are not able to multiply, they promote an environment that can lead to relapse.

The aim of a previously funded preclinical study at the University of Birmingham is to develop a new type of immune cell therapy that controls both tumour growth, and also targets senescent cells to prevent relapse. The study has shown promising preliminary data and is ready to move on to the next stage towards clinical trial ‘readiness’.

Engineering natural killer (NK) cells

The immune cells used in this study are natural killer (NK) cells. Unlike T-cells they don’t need to be “trained” to recognise cancer cells, so they can detect and remove abnormal cells more quickly. The NK cells will be engineered to recognise more than one target on the surface of DMG cells and increase the immune system's ability to eliminate cancer cells. One target is the GD2 protein that is present on many DMG cells, and has been the target of previous CAR T-cell therapies. The other target is created during radiotherapy and essentially marks the abnormal cells for elimination. As this new therapy will also increase the immune system’s activation, it will lead to a powerful multiway attack against DMG tumours.

By attacking the DMG tumours from three different angles we can overcome the biggest challenge during brain cancer treatment, treatment resistance.

An additional benefit of this therapy is that it doesn’t require lengthy cell preparation and the NK cells are designed as “off-the-shelf” therapy, ready to use when needed. This will help with another challenge of the DMG treatment, that is accessing treatment for this rapidly progressing cancer. We hope that this “ready-to-go” immune cell therapy can treat more children quickly enough for meaningful help.

Expert Team

Dr Ashley Vardon - NIHR Academic Clinical Lecturer, Institute of Cancer and Genomic sciences, University of Birmingham.

The team is working with Cell and Gene Therapy Catapult and industry to scale manufacturing and ensure it can be delivered within a national healthcare system.

The goal is to translate this from laboratory concept to clinical trial within the next two years.

Next steps with this new funding will be in two parts and includes generating and optimising these new NK cell therapy constructs and testing the method in animal models.

If successful, the latter work will be led by Professor Chris Jones at The Institute of Cancer Research using post-radiotherapy conditions to mimic the senescent cell environment. (in a further funding agreement) At this stage our follow-on funding covers the cost of a Research Assistant and Post-Doctoral Research Associate, for the required experiments to help move the study forward in preparation for eventual clinical trial testing.

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