Four children with terminal brain cancer saved by new cell therapy

Four children with traditionally incurable brain cancers are still alive years after receiving an experimental immune-boosting cell therapy in a clinical trial. Three of them even display no evidence of disease. “These children are getting to grow up – it’s truly awesome,” says Gene Hwang at Children’s National Hospital in Washington DC. The experimental treatment, called tumour-associated antigen (TAA) T-cell therapy, was given to 33 children and young adults with either newly diagnosed diffuse intrinsic pontine glioma (DIPG), a highly aggressive form of brain cancer, or other brain tumours that hadn’t responded to standard treatments. The trial focused on these tumour types because “they’re universally fatal, there’s nothing else for them”, says team member Catherine Bollard, also at Children’s National Hospital. Advertisement Children with DIPG typically survive for less than a year, but one of the treated children with this condition is still alive more than two years after receiving the TAA T-cell therapy. Among the participants with other kinds of brain tumours, three responded remarkably well to the therapy. They had aggressive forms of recurrent glioblastoma, astroblastoma or medulloblastoma and had previously gone through up to 17 rounds of treatments like chemotherapy and radiation that had been unsuccessful. Since receiving the TAA T-cell therapy, the three children are alive with no evidence of disease between two and five years on. “I’m still in contact with one of the families and they’re unbelievably grateful that their child is still with them today,” says Bollard. The trial was small and didn’t include a control group to compare the therapy with standard treatment, but 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”. It is still unclear why the treatment worked for some children but not others, she says. “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. The therapy involves taking a sample of a person’s blood, collecting immune cells called T-cells and essentially training them in a lab to target three protein markers, known as antigens, that are commonly found in paediatric brain tumours, says Bollard. This is done by exposing the T-cells to other cells that present these antigens, then selectively multiplying the T-cells that recognise them. The multiplied T-cells are then returned to the person intravenously, so their own immune system becomes better at fighting their cancer. TAA T-cell therapy is different to CAR T-cell therapy, which is now widely used to treat blood cancers, but generally lacks efficacy against solid tumours. In CAR T-cell therapy, people’s T-cells are genetically engineered to give them synthetic receptors called chimeric antigen receptors, which help them detect single antigens on cancer cells, usually those in blood. In contrast, TAA T-cell therapy involves no genetic engineering, allows targeting of multiple cancer antigens and may work more broadly for solid tumours. So far, TAA T-cell therapy seems to have fewer side effects than CAR T-cell therapy, perhaps because it doesn’t genetically modify a person’s T-cells, says Bollard. In the trial, most patients tolerated the therapy well, with fatigue and headache being the most common side effects. Two people experienced tumour swelling, but this may have been because they already had large tumour volumes, says Bollard. The team is now beginning two more clinical trials of the therapy for children with brain tumours. In one, the TAA T-cell therapy will be combined with an ultrasound technique that opens the blood-brain barrier to hopefully allow more of the T- cells to get into the brain. In the other trial, each patient’s tumour will be genetically sequenced to identify its unique antigens, allowing their T-cells to be specifically trained to target these antigens in a personalised way. “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. Nature Medicine DOI: s41591-026-04449-9