A hopeful step is emerging for children facing some of the hardest-to-treat brain cancers.
In a small clinical trial at Children’s National Hospital in Washington DC, four children with brain tumours long considered incurable are still alive years after receiving an experimental immune-based treatment. Even more heartening, three of them currently show no evidence of disease.
“These children are getting to grow up – it’s truly awesome,” says Gene Hwang at Children’s National Hospital.
The treatment, known as tumour-associated antigen T-cell therapy, or TAA T-cell therapy, is designed to help a patient’s own immune system recognise and attack cancer cells. It was tested in 33 children and young adults with either newly diagnosed diffuse intrinsic pontine glioma, known as DIPG, or other brain tumours that had not responded to standard care.
DIPG is an especially aggressive childhood brain cancer, and children diagnosed with it usually survive for less than a year. In this trial, one child with DIPG is still alive more than two years after receiving the therapy.
The study also included children with other severe brain cancers, including recurrent glioblastoma, astroblastoma and medulloblastoma. Three of these children had especially strong responses. Before joining the trial, they had already received as many as 17 rounds of treatments such as chemotherapy and radiation, without success. After TAA T-cell therapy, they remain alive with no evidence of disease between two and five years later.
“I’m still in contact with one of the families and they’re unbelievably grateful that their child is still with them today,” says Catherine Bollard, also at Children’s National Hospital.
The trial was an early phase-I safety study, meaning it was small and did not include a control group for comparison. Still, the results have brought cautious optimism. Bollard says “we’re very excited because, although it was only a phase-I safety study, there did seem to be a signal of efficacy”. Researchers do not yet know why some children benefited so strongly while others did not.
The children in the study had cancers chosen because of their extreme severity. The trial focused on these tumour types because “they’re universally fatal, there’s nothing else for them”, says Bollard.
Other experts are encouraged, while also emphasising that more research is needed. “No one is jumping up and down and saying ‘this is it’ just yet, but it is encouraging and it’s one step further along in our understanding of how to use cellular therapies to attack brain tumours,” says Tim Hassall at Queensland Children’s Hospital in Australia.
TAA T-cell therapy begins with a blood sample from the patient. Scientists collect immune cells called T-cells and train them in the laboratory to recognise three protein markers, or antigens, commonly found in childhood brain tumours. The T-cells that respond to these antigens are then multiplied and infused back into the patient through a vein. The goal is to give the child’s own immune system a stronger ability to fight the cancer.
This approach differs from CAR T-cell therapy, which has been highly successful for some blood cancers but has generally been less effective against solid tumours. CAR T-cell therapy genetically engineers T-cells to detect a single cancer antigen using synthetic receptors. TAA T-cell therapy does not involve genetic engineering and can train the cells to target multiple tumour antigens, which may make it useful for a wider range of solid tumours.
The treatment also appears, so far, to have fewer side effects than CAR T-cell therapy. In this trial, most participants tolerated it well. The most common side effects were fatigue and headache. Two people experienced tumour swelling, which Bollard says may have been related to already having large tumour volumes.
The research team is now moving forward with two additional clinical trials for children with brain tumours. One will combine TAA T-cell therapy with an ultrasound method intended to temporarily open the blood-brain barrier, with the hope of helping more T-cells reach the brain. The other will use genetic sequencing of each patient’s tumour to identify its unique antigens, allowing scientists to train that child’s T-cells in a more personalised way.
For families and doctors who have long had few options, the work represents a welcome opening. “For the last 20 or so years, we haven’t really moved the dial in terms of improving survivability for these paediatric brain tumours, so it’s exciting to have a whole different treatment area opening up,” says Hassall.
