First-of-its-kind clinical trial at GOSH gives hope of treatment for notoriously difficult to treat childhood cancer
5 Sep 2022, 9 a.m.
Researchers at University College London (UCL) and Great Ormond Street Hospital (GOSH) hope to develop a new treatment for an aggressive type of brain tumour, diffuse midline glioma (DMG), until recently known as diffuse intrinsic pontine glioma (DIPG), using a patient’s own immune system to attack the cancer cells. This form of cancer currently has some of the worst outcomes for children.
A £1.2million grant from Great Ormond Street Hospital Children’s Charity (GOSH Charity) has been awarded to the team, which is being led by Dr Karin Straathof, Associate Professor at the UCL Cancer Institute and Honorary Consultant at GOSH. Dr Straathof will be collaborating with GOSH Charity Clinical Professor in Paediatric Neuro-Oncology and Honorary Consultant at GOSH, Professor Darren Hargrave and the team will use CAR T-cells (patient immune cells engineered to recognise and eradicate cancer cells) in a clinical study for up to 12 patients with DMG at GOSH.
CAR T-cell therapy has previously been used to successfully treat some childhood leukaemias and this team have also used the technology in clinical study for patients with neuroblastoma, a rare cancer that develops in nerve cells. They killed neuroblastoma cells by engineering T-cells to target a specific protein called GD2, and this protein is also found on the surface of DMG cancer cells, making it their next focus.
While treatments for some childhood cancers have developed significantly over the last few decades, there has been little progress for children with DMG, with most patients dying within two years of diagnosis. Brain tumours are the most common cause of cancer-related death in children, and brain tumours located deep in the brain are particularly difficult to treat. The most aggressive of these tumours is DMG, which carry the worst prognosis.
DMG develops in important parts of the brain that control bodily function. The tumour cells also become mixed with normal brain cells rather than a defined tumour, which means that removing the cancer via surgery is impossible. Although radiation therapy can sometimes temporarily halt the tumour growth, it unfortunately usually grows back, often more aggressively.
With results from a study at Stanford University in the USA already showing promise of CAR T-cell therapy in DMG, it is hoped that this clinical trial at GOSH will be a crucial first step in developing effective CAR T-cell treatments for DMG and other high-risk brain tumours that can be devastating to families.
Dr Karin Straathof, who is leading this research, said: “Despite huge advancements in childhood cancer treatments and care, many cancers are still extremely difficult to treat. There are currently no licensed treatments for DMG different to radiotherapy or chemotherapy. A DMG diagnosis can be devastating for families, so we hope that this trial brings us one step closer to developing a viable, effective treatment for children with DMG.”
Professor Darren Hargrave said: “DMG is the most difficult and challenging childhood cancer we face, with a dismal prognosis and novel approaches are desperately required. Harnessing the body’s own immune cells by using engineered CAR T-cells and using these as a “living drug” to try to attack DMG, is such a novel approach. This first trial, in the UK, is a vital initial step to see if we can make an impact in this terrible disease.”
GOSH Charity’s Director of Impact and Charitable Programmes, Dr Kiki Syrad, said: “The fact that there are still some types of childhood cancer with such a low survival rate proves just how crucial research, like this study looking into new treatment options for DMG, is. The Charity is so proud to be supporting this important study, which provides some much-needed hope for a cancer with one of the worst outcomes for children.”
GOSH Charity’s grant for this clinical trial was made possible thanks to donations from The Lyla Nsouli Foundation for Children’s Brain Cancer Research, Funding Neuro, Abbie’s Army, CRIS Cancer Foundation and The Azaylia Foundation. It is hoped that up to 12 children with DMG at GOSH will be able to enroll and be treated with the therapy as part of the clinical trial that will start in early 2023.
Simone and Nadim, Founders of The Lyla Nsouli Foundation, had a daughter, Lyla, who was born on Christmas Eve 2008. After a natural birth with no complications, she was assessed as a healthy baby and was doted on by her parents. During a family holiday and aged just two years old, Lyla was diagnosed with DIPG, an untreatable, aggressive brain cancer.
Simone said: “Lyla was a normal, healthy, gregarious child, full of energy who talked very early on and who always loved to sing and dance. She would entertain any visitor to our home with exuberant singing and dancing and, as soon as she could speak, she demonstrated an amazing ability to remember the words and melodies of many songs.”
Lyla was enjoying her childhood and was about to become a big sister when her parents started noticing some changes in her behaviour.
“In the months before her diagnosis, there were some changes in Lyla. Looking back now, these changes may have been early indications that something was wrong, but she was in her ‘terrible two’s’ stage and becoming aware of the arrival of a new sibling, so it was difficult to relate them to a sinister illness.”
It wasn’t until a family holiday in August 2011 that Lyla’s family knew something was wrong. “We had just spent a wonderful holiday in Spain with her young cousins and we woke up early to catch a flight to Nice. We noticed that she was dragging her left foot, but she wasn’t complaining of any pain or discomfort.
“We decided we would find a local doctor when we arrived in France but, after a short flight, only hours later, we were alarmed to see it had worsened and took her straight to the hospital. A doctor’s examination determined that her entire left side was weak. After she did an MRI, we were told that a neurologist was coming to speak to us about ‘abnormalities’ they had discovered. It was an excruciating wait full of panic and overwhelming fear.”
Nadim and Simone were then taken to a doctor’s office and told that Lyla had DIPG. She only had months to live.
“The words were like painful, physical blows, difficult for the mind to assimilate and causing such extreme anguish that our reactions ranged from numb disbelief to absolute hysteria. In that moment, our lives changed forever.”
Lyla and her family came home from France and were immediately taken under the care of GOSH. “As soon as we arrived at GOSH, we just felt like we were in a safe place. It felt like all of the staff there genuinely understood our situation and were very capable and willing to do everything they could to help.”
Within days of her diagnosis, Lyla started intensive radiotherapy, the only treatment option available which offered a small possibility of delaying her decline by weeks or months. “The six weeks endured for her radiotherapy were absolute heart-wrenching agony. Each day brought fear, pleading, screaming and rage from Lyla and total anguish and heartbreak for us. She was also on a high dose of steroid medication which caused manic mood swings.
“Lyla’s eyes became dull, heavy and sad. It was as if their lights of joyful exuberance and childish innocence, were completely dimmed and darkened.”
Despite its intensity, Lyla’s radiotherapy treatment only gave her an extra two months, during which time the family went on their favourite beach holiday and to Disneyland Paris. Shortly after Lyla’s third birthday, the family were told that the tumour had started growing aggressively again.
Lyla’s condition deteriorated very quickly and she passed away in the early hours of the 24th January 2012 in the arms of her parents.
On the importance of research into childhood cancer, Simone said: “Research like this is vitally important and the difference in research funding between adult’s and children’s cancers is just shocking. Childhood cancer is consistently underfunded despite the fact that cancer is the leading cause of death for children from disease. Children with cancers like DIPG, are dying every day because there are no effective treatment options available, due to decades of underfunding and slow progress. How can that be conceivable? We need research that is dedicated to children’s cancer because we can’t use adult solutions on children; they don’t work and can be harmful.
“Furthermore, investing in children’s cancer research is vitally important for cancer treatment in general because it requires the development of new, more advanced alternatives to chemotherapy and radiotherapy, which have been the standard of treatment for decades.
“DIPG is one of the most devastating childhood cancer diagnoses and one that my family had to painfully endure. It hasn’t had the attention it desperately needs so funding research like this CAR-T clinical trial is vital and we hope it will offer those affected by DIPG some much needed hope.”
Anna and Louis’s story
On the 3rd May 2014, the Brooks family received the worst possible news, their beautiful and much-loved six-year-old daughter Daisy had been diagnosed with DIPG.
Daisy went from being a normal child at school one day, with no sign of illness, to hospital the next. She started having radiotherapy the following week.
Daisy’s parents were told that there was no hope of a cure, but that radiotherapy would hopefully buy a little extra time to make precious memories with their daughter. The family were told that, if they were lucky, they could expect a few weeks before the symptoms would take hold and their little girl would start to slip away.
Like any parents in this situation, Anna and Louis desperately searched the globe for treatment options and were shocked to discover how few trials there were for this devastating illness, especially in the UK. Daisy was eventually offered the chance to undergo experimental surgery and, although it wasn’t enough to save her, alongside Daisy’s incredible bravery and spirit, it gave her a few precious extra months with her family before passing away on her 7th birthday. Anna and Louis have since gone on to raise a considerable amount in Daisy’s memory to fund research into treatments to beat DIPG.
Anna and Louis know how vital it is that more treatment options are available to treat children who are given a devastating DIPG diagnosis. They hope that one day a cure will be found, and that no more families have to suffer the loss of a child like they did.
Statement – 12th September
The team at GOSH understands the impact of a DMG diagnosis, both on the patient and their loved ones. Hence we are working very hard to bring innovative and novel therapies forward to the clinic as soon as we can.
However, such novel therapies remain experimental and need to be given only in the setting of an approved and regulated clinical trial. With required funding in place, the GD2 CAR-T cell therapy study is now going through all the necessary reviews and approvals with the expectation that it will be open in early 2023. As soon as the trial is open for recruitment, we will make contact with all of our UK colleagues to inform them that we are ready to consider patients to take part in this study.
It is important to be aware that an assessment is required to see if a patient can take part in the clinical trial. This study will recruit:
- Patients with a brainstem or spinal diffuse midline glioma proven by a biopsy.
- Newly diagnosed patients who have or will undergo standard radiotherapy treatment and have not relapsed.
- Patients who are eligible to receive NHS treatment from the UK.
- Patients who meet all other study eligibility criteria as assessed by the patient’s local and the GOSH study team.
Due to the experimental nature of this therapy and safety regulations, there will be limits as to how many patients can be treated at the same time.
We thank everyone for their interest and will update as soon as the study is ready to open.
For more information, please contact:
Grace Waters, GOSH Charity press office
020 3841 3237 / email@example.com
Notes to Editors
Notes to editors
About Great Ormond Street Hospital and Great Ormond Street Hospital Children’s Charity:
Great Ormond Street Hospital is one of the world’s leading children’s hospitals with the broadest range of dedicated, children’s healthcare specialists under one roof in the UK. The hospital’s pioneering research and treatment gives hope to children from across the UK with the rarest, most complex and often life-threatening conditions. Our patients and families are central to everything we do – from the moment they come through the door and for as long as they need us.
Great Ormond Street Hospital Children’s Charity needs to raise money to support the hospital to give seriously ill children, the best chance for life. The charity funds research into pioneering new treatments for children, provides the most up to date medical equipment, funds support services for children and their families and supports the essential rebuilding and refurbishment of the hospital. You can help us to provide world class care for our patients and families. For more information visit www.gosh.org
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