CANCER RESEARCH UK scientists at the University of Southampton have developed a potential new antibody treatment which, in the laboratory, shows significantly increased survival from neuroblastoma – a form of childhood cancer which grows from undeveloped tissue of the nervous system. It is hoped that it could one day be used to treat children with the disease. Their findings will be presented at the NCRI Cancer Conference in Birmingham today (Monday).
The researchers have developed two monoclonal antibodies (mAbs) called anti-4-1BB, anti-CD40, and 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 recognise the response that the immune system produces and stimulate it, so that it is more effective in attacking and killing cancer cells.
They 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 significantly slow tumour growth, 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 recognise the cancer cells.
The three monoclonal antibodies were tested independently and will be developed by the scientists to see if they can improve them further.
Neuroblastoma is a solid form of tumour that normally develops in the abdomen. It affects around 100 children in the UK each year – most cases are diagnosed under the age of five.
Dr Juliet Gray, clinical lecturer in oncology at the University of Southampton, and a paediatric oncologist at Southampton General Hospital, who will present the findings at the NCRI Cancer Conference, said: “Although this work is still at a pre-clinical stage, we hope it has enabled us to identify a way that we can provide effective immunotherapy treatment against neuroblastoma. More research is needed to understand how these antibodies work and how they should be used to treat neuroblastoma. We then hope to take the approach into a phase 1 clinical trial in children with this disease.
“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.”
Although immunotherapy is a relatively new form of treatment, a number of monoclonal antibodies are licensed to treat adult cancers or are in clinical trials. Similar approaches which use mAbs to trigger the immune system to attack and kill cancer cells include Rituximab for non Hodgkin’s lymphoma (NHL) and some types of leukaemia and Alemtuzumab for chronic lymphocytic leukaemia (CLL). Another potential antibody treatment called anti-GD2 – which uses a slightly different method of tackling the disease – has also shown promising results for neuroblastoma in clinical trials.
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: “We very much hope these results will enable us to develop a pioneering immunotherapy treatment for a childhood cancer. 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.”
Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “This is exciting work but it’s very early days. If the promise of immunotherapy holds true in clinical trials in children it will give us another option to use in the fight against neuroblastoma.”
Combining peptide vaccination with immunostimulatory monoclonal antibodies provides potent immunotherapy in neuroblastoma: Dr Juliet Gray, NCRI Cancer Conference.
This work also received funding from the Wessex Medical Research.
About therapeutic monoclonal antibodies
Monoclonal antibodies (mAbs) are a type of biological therapy. They are designed to recognise 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 may:
• Trigger the immune system
• Stop cancer cells from taking up proteins
• Carry cancer drugs or radiation to cancer cells
This research is on monoclonal antibodies that trigger the immune system.
You can out more about monoclonal antibody treatments on Cancer Research UK’s patient information website CancerHelp UK
Neuroblastoma is the most common solid tumor that develops outside the head among children and is the most common cancer among infants. Childhood cancers have been ranked using single types of tumour.
It develops from immature nerve tissue. Neuroblastoma often starts in the tummy (abdomen), commonly in the adrenal glands or the nerve tissue at the back of the abdomen. But it can spread to other parts of the body, such as the bones, liver and skin, through the blood and lymphatic system.
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).
Symptoms can be vague at first, such as tiredness, fever and loss of appetite. This can make neuroblastoma hard to diagnose in the early stages.
Because neuroblastoma usually develops in the abdomen, the most common symptom is often a lump in the tummy. This may make the child’s tummy swell, causing discomfort or pain. Sometimes neuroblastoma can appear as a lump in the neck, perhaps causing breathlessness or difficulty in swallowing.
Most children with neuroblastoma have higher than normal levels of catecholamines which is what doctors test for.
Find out more about neuroblastoma on Cancer Research UK’s patient information website CancerHelp UK