T cell therapy linked to long-term remissions in children with brain tumours

An experimental autologous T cell therapy has shown encouraging early results in children with aggressive brain tumours.

Conventional targeted therapies for brain and spinal cord tumours often target a single tumour-associated protein, allowing cancer cells lacking that target to survive and potentially drive disease recurrence. Researchers based at Children's National Hospital in Washington DC have now developed a T cell therapy that 'trains' patients' own immune cells to recognise three tumour-associated proteins simultaneously. Unlike CAR T cell therapy, this multi-target immune therapy approach does not involve genetically modifying the patient's T cells.

'This study represents an important step toward developing safer and more effective T cell therapies for children with devastating brain cancers,' said Dr Catherine Bollard, senior vice president and chief research officer at Children's National Hospital. 'Even in this early-stage trial focused on safety, we were encouraged to see lasting clinical benefit in several patients who otherwise had very few options.'

Brain and spinal cord tumours are the second most common childhood cancers, accounting for more than 25 percent of paediatric cancer cases in the UK. Childhood brain cancers such as diffuse intrinsic pontine glioma (DIPG) and recurrent brain tumours have limited treatment options and poor survival.

In the Phase 1 trial, researchers collected patients' own T cells and expanded them in the laboratory by exposing them to antigen-presenting cells (APCs) carrying three tumour-associated proteins (WT1, PRAME and survivin). APCs are a specialised type of immune cell that 'catch' and present protein markers to T cells, helping the immune system to identify threats. The resulting T cells were then infused back into the patients to target tumour cells expressing these proteins.

The therapy was generally well tolerated and showed encouraging signs of clinical activity. Among children with DIPG, two patients experienced prolonged survival of 32 and 21 months, respectively, with the latter remaining alive at the latest follow-up, substantially longer than is typically seen with the disease.

Among children with recurrent brain tumours, three were alive without disease at 31.8, 41.2 and 51.6 months after treatment without further anticancer therapy. One child with a rare brain tumour called astroblastoma had no detectable evidence of disease one year after completing three infusions of the T-cell therapy and remained disease-free three years later.

'We were excited to see that we could preserve safety and quality of life while generating anti-tumour responses by attacking three targets at once,' said Dr Eugene Hwang, chief of the division of oncology at Children's National Hospital and co-senior author of the study published in Nature Medicine.