Introduction

GOSH Charity is the official charity of Great Ormond Street Hospital, a leading children’s hospital that combines highly specialised patient care with world-class research.

One of the key priorities of the research supported by GOSH is childhood cancer. To address this, the charity funds a range of strategic projects and runs initiatives to identify innovative research with the potential to transform treatment outcomes, particularly for the most aggressive forms of cancer.

This commitment to advancing research has led to a collaboration between CRIS Cancer Foundation and GOSH. Together, they are supporting a clinical trial focused on a particularly devastating type of childhood brain cancer: diffuse midline glioma (DMG).

This trial involves the use of GD2-targeted CAR-T therapy in paediatric patients diagnosed with diffuse midline glioma, an aggressive and currently incurable disease, and is co-funded by CRIS Cancer alongside other partner organisations.

The Project

Diffuse midline glioma is a rare type of brain tumour that occurs more frequently in children than in adults. It develops in the central region of the brain, particularly within the brainstem and surrounding structures, which is reflected in its name.

At present, these tumours are unfortunately incurable and carry a devastating prognosis. Most children die within the first year following diagnosis, and fewer than 10% survive beyond two years.

This clinical trial, led by Dr Karin Straathof at the Great Ormond Street Institute of Child Health in London, will use CAR-T technology for the first time to target this type of tumour. CAR-T therapy involves collecting a patient’s own immune cells (T lymphocytes) and genetically engineering them to express a molecular “detector” that enables them to recognise and destroy cancer cells.

In this case, the engineered cells are designed to target GD2, a molecule commonly found on DMG tumour cells but rarely present on healthy tissue. The trial will include 12 children, all of whom will receive GD2-targeted CAR-T therapy.

Thanks to the support of CRIS Cancer Foundation, GOSH and other partner charities, this pioneering project, the first clinical trial in Europe to apply CAR-T therapy to a brain tumour, has the potential to open the door to far more effective treatments for a cancer that currently has no viable therapeutic options.

Recent Progress

In recent months, Dr Straathof’s team has successfully completed the full regulatory phase required before launching the clinical trial. This is a critical and necessary step, as any therapy being used in humans for the first time must meet strict preliminary requirements, involve extensive documentation, and receive approval from relevant regulatory authorities and ethics committees.

All required approvals have now been secured, allowing the trial to proceed.

As a result, patient recruitment has already begun. Over the past year, five children with diffuse midline glioma have been enrolled in the trial. Although it is still too early to assess treatment effectiveness, the therapy has been shown to be safe so far.

In parallel, researchers are closely studying how the CAR-T cells behave in the body, specifically whether they reach the tumour, how they interact with tumour cells, and what immunological processes occur during treatment. These insights will be essential for refining this therapy and informing the design of larger trials in the future.

The trial is progressing well, and if results continue to meet expectations, this work, supported by CRIS Cancer Foundation, could represent an important first step toward developing safe and effective CAR-T therapies for brain tumours, an area that remains largely unexplored.