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Hope for pioneering immunotherapy treatment for childhood cancer

Cancer Research UK scientists at the University of Southampton have developed a potential new antibody treatment that, in the laboratory, shows significantly increased survival from neuroblastoma, a form of childhood cancer that grows from undeveloped tissue of the nervous system.

It is hoped that the treatment could one day be used to treat children with the disease. The scientists’ findings were presented at the NCRI Cancer Conference in Birmingham last Monday.

The researchers have developed two monoclonal antibodies (mAbs) called anti-4-1BB and anti-CD40 (and have investigated a third, called anti-CTLA-4), which bind to molecules in the immune system. It is hoped that these antibodies can be used to boost or 'super charge' the body's immune system to help it fight cancer.

The body's immune response is generally much weaker to cancer than it is to infections, and in most cases, it does not stop tumours from growing. These antibodies are designed to recognize the response that the immune system produces and stimulate it, so that it is more effective in attacking and killing cancer cells.

The researchers found that 40 to 60 per cent of the tumours treated with the stimulatory antibodies were destroyed in laboratory models. With more aggressive tumours, the antibodies alone did not slow tumour growth significantly; however, when the researchers paired one of the monoclonal antibodies with a peptide called Survivin, a similar survival benefit was seen. Survivin is a good immunotherapy target because it is present in 80 to 100 per cent of neuroblastoma tumours but rarely seen in normal tissue. Peptides work by training the immune system to recognize the cancer cells.

The three monoclonal antibodies were tested independently and will be developed by the scientists to see whether they can improve them further.

Dr Juliet Gray, clinical lecturer in oncology at the University of Southampton and a paediatric oncologist at Southampton General Hospital, who presented the findings at the NCRI Cancer Conference, said: ‘Six out of ten children with neuroblastoma can be successfully treated with conventional chemotherapy. But for those children who don't respond well to this treatment, immunotherapy could become a vital new treatment option.’

Cancer Research UK's Professor Martin Glennie, director of the Cancer Sciences Division at the University of Southampton School of Medicine, who also worked on the study, said: ‘In theory this approach enables us to kill cancer cells without damaging healthy cells, resulting in fewer toxic side-effects such as hair loss, nausea and tiredness.

‘The next stage of our work will be to see if the treatment is a safe and effective treatment for children and also seek to understand how these antibodies can be used in combination with other treatments to maximise their effect.’

Monoclonal antibodies (mAbs) are a type of biological therapy. They are designed to recognize and bind to specific proteins on cells. Each monoclonal antibody recognises one particular protein. There are three main types of therapeutic monoclonal antibodies that work in slightly different ways. They might trigger the immune system, stop cancer cells from taking up proteins, or carry cancer drugs or radiation to cancer cells. This research is on monoclonal antibodies that trigger the immune system.

Neuroblastoma is a solid form of tumour that normally develops in the abdomen. It affects approximately 100 children in the UK each year, and most cases are diagnosed under the age of five. It develops from immature nerve tissue, but it is not known exactly what causes neuroblastoma. In some cases, there is a family history of neuroblastoma, but these cases are very rare (1 in every 100 diagnosed).

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