Immune cells, known as Natural Killer T cells, could be redirected to help fight the childhood cancer, neuroblastoma, according to research presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool.

By genetically modifying human Natural Killer T (NKT) cells so that they recognise neuroblastoma cells as being dangerous, researchers managed to achieve long-lasting remission - and in some instances cures - of mice that carried highly aggressive human neuroblastoma.

NKT cells are specialised immune cells which respond quickly to danger, such as an infection or tumour growth, and help kick-start an immune response to protect us.

The researchers, from the Texas Children’s Cancer Center and Center for Cell & Gene Therapy at the Baylor College of Medicine, have harnessed this ability of NKT cells to act as a warning siren by genetically engineering them to react to a molecule often found on the surface of neuroblastoma tumours known as GD2. It is thought that these modified NKT cells will kill the tumour cells and also reactivate local immune cells that have been tricked into ignoring or even supporting the cancer.

Leonid Metelitsa, professor of paediatrics and immunology at Texas Children’s Cancer Center, said: “Tumours often find ways to avoid the immune system or ‘switch it off’ in order to grow and survive, so any way we can switch the immune system back on and redirect it towards cancer cells would be a significant advance. By modifying these Natural Killer T cells so that they target neuroblastoma tumours and sound the alarm for the rest of the immune system we hope to have developed a new approach to treating this disease.”

Neuroblastoma develops from nerve cells left over from a baby’s development and there are around 100 children diagnosed with the cancer each year in the UK. Despite the number of children surviving neuroblastoma rising from 17 per cent in 1971 to 64 per cent today, the aggressive form of the disease is still very hard to treat successfully.
 

Dr Harpal Kumar, chief executive of Cancer Research UK and chair of the NCRI, said: “We are excited to see so much research both here and internationally into badly needed new treatments for neuroblastoma patients. Cutting edge research, such as this study, together with Cancer Research UK’s newly opened trials, are making a vitally important step towards better and kinder treatments for children with neuroblastoma.”

Dr Louis Chesler, Head of the Paediatric Solid Tumour Biology and Therapeutics team at The Institute of Cancer Research, said:
“Neuroblastoma is one of the most common solid tumours of children and is still very difficult to cure in high-risk form.

“The introduction of immune therapy, using an antibody targeted to GD2, a molecule present on the surface of neuroblastoma tumour cells, is among few interventions to have produced a measurable increase in long-term survival of patients with the high-risk form of this disease.

“Advanced immunotherapeutic approaches, involving the use of engineered antigen receptors and T or NKT cells, represent a significant step forward in harnessing the potential of immune therapy for neuroblastoma.

“There are still practical issues relating to the efficient generation of these therapeutics for clinical use, but no doubt these will be rapidly dealt with as these approaches become effective for other cancers. The use of these techniques should now be addressed through pilot studies in the early-phase clinical setting.”

Source: NCRI