New hope for children with aggressive form of cancer

Children with an aggressive form of cancer are being given new hope in a world-first trans-Atlantic clinical trial that will test a new three-part treatment.

The study, involving doctors and cancer scientists in Southampton, America and Germany, will boost the body's immune system to kill off neuroblastoma, one of the most common childhood cancers.

The Phase 1 trial is funded by UK charities Solving Kids' Cancer (Europe), JACK and US charities Solving Kids' Cancer and Band of Parents. It will be one of many to be conducted at the University of Southampton's Centre for Cancer Immunology, which is the UK's first and only centre dedicated to cancer immunology research. The centre recently opened at University Hospital Southampton, thanks to the University's £25m fundraising campaign.

Neuroblastoma affects around 100 children - mostly under the age of five - in the UK every year and develops from immature nerve cells. It usually starts as a tumour in the abdomen or chest, however, in many children, it spreads to other places in the body such as the bones and bone marrow.

In those cases, less than half of patients are cured despite intensive treatment which includes surgery, chemotherapy, radiotherapy and stem cell transplants.

More recently, a form of immunotherapy known as anti-GD2, which uses antibodies to lock onto cancer cells so the immune system can find, fight and destroy them, has shown the potential to improve survival rates.

This new study, led by Dr Juliet Gray, Associate Professor of Paediatric Oncology at the University of Southampton, involves combining mIBG, a special form of targeted radiotherapy which delivers radioactive iodine directly to neuroblastoma cells, with two different antibody therapies for the first time.

One of these therapies, Nivolumab, has shown exciting results in adult cancers. It blocks a harmful protein called PD-1 and gives patients' own immune cells a boost so that they can be set free to kill tumour cells.

The researchers will give Nivolumab alongside the currently-used anti-GD2 to target specific cancer cells while protecting normal healthy cells.

The trial will be run from four centres - the University of Southampton's Centre for Cancer Immunology, UCH, Madison Children's Hospital, Wisconsin, and the University of Greifswald, Germany. It is also the first trial to be sponsored by University Hospital Southampton NHS Trust.

"Immunotherapy with anti-GD2 has been shown to increase the number of children with neuroblastoma who stay in remission and has become a standard component of treatment - but sadly a large number of children still relapse and die from their disease," explained University of Southampton's Dr Gray who is also a consultant paediatric oncologist at Southampton Children's Hospital.

"Work in the laboratory has shown that combining these types of antibodies with radiotherapy is potentially a very powerful way of eradicating neuroblastoma tumours and these three different therapies appear to work together to generate strong, protective immunity to the tumour."

She added: "This trans-Atlantic trial will be the first time they have been tested together and we are hopeful the combination of treatments will substantially improve the cure rate of children with this form of cancer."

Stephen Richards, CEO of Solving Kids' Cancer (Europe), said: "Cutting-edge clinical trials offer real hope for children with high-risk neuroblastoma and their families. The numbers of children affected are small, so funding collaborative international research is the only way we will improve survival rates and find a cure for this devastating disease."

The researchers plan to give an initial course of mIBG-targeted radiotherapy followed by Nivolumab and anti-GD2 over a period of six months. Although the initial stages of the treatment process will require children to be in hospital, it is hoped that the therapy will be well tolerated and will eventually be delivered largely on an outpatient basis.

The trial's objective is to ensure the combination is safe to deliver to children with neuroblastoma in order to develop further studies to compare it with current treatments.