Immunotherapy for high-risk neuroblastoma

01 June 2012

Professor John Anderson, UCL Institute of Child Health, London

Neuroblastoma is one of the most common childhood tumours. It has a high-risk form that is one of the most difficult childhood cancers to cure, despite intensive therapy. This project aims to harness a new immunotherapy approach to develop a treatment strategy for high-risk neuroblastoma that is more effective and less toxic than current approaches.

Amount of grant: £151,195*  |  Date of award: June 2012

The team
Professor John Anderson, Dr Martin Pule & Dr Karin Straatfhof, UCL Institute of Child Health; Professor Louis Chesler, Institute of Cancer Research; Professor Kerry Chester, UCL Cancer Institute.


Neuroblastoma – a nerve tumour - is one of the most common childhood cancers, with around 100 children diagnosed every year in the UK. Most of these children are under the age of five years.

Around 40 per cent of children diagnosed with neuroblastoma have a high-risk form that is essentially incurable using conventional treatments (chemotherapy, radiotherapy, surgery). Not only do these children have a very poor chance of survival, but those who do survive suffer major long term toxicity as a result of the toxic treatments that currently represent their only chance of survival. The toxicities include infertility, kidney and hearing impairment and increased risk of second cancers.

Immunotherapy approaches are now being used with a great deal of success in the treatment of a range of cancers. Cancer immunotherapy attempts to stimulate the patient’s immune system to reject and destroy tumours.

Immunotherapy is still in its infancy for the treatment of childhood cancers but a recent clinical trial has shown some success in the treatment of neuroblastoma. The immunotherapy treatment targets a protein called GD2 that is present on the surface of neuroblastoma cells. This approach increased survival by 15 per cent in high risk patients. However this anti-GD2 therapy, which is given in addition to conventional treatments, is highly toxic since GD2 is also present in normal cells and tissues.

A new immunotherapy approach

In this project the research team is aiming to improve on current immunotherapy for neuroblastoma in terms of both increasing efficacy and reducing toxicity.

They will target an alternative molecule called ALK. ALK is a newly identified protein that is present on the surface of neuroblastoma cells from most patients with the disease. Importantly, however, ALK is absent from normal cells meaning that targeting of ALK would not result in the toxicity that is seen with anti-GD2 therapy.

The research team is uniquely placed to carry out this work. Professor John Anderson, a paediatric oncologist at Great Ormond Street Hospital (GOSH), is one of the country’s leading experts on neuroblastoma, from both a clinical and a scientific perspective. His colleagues on this project, from within GOSH, from UCL Institute of Child Health, the UCL Cancer Institute and the Institute of Cancer Research at the Royal Marsden, bring crucial expertise in different aspects of the proposed work.

This is an excellent team of co-applicants – combining international expertise in antibody technology, neuroblastoma modelling, and paediatric translational immunotherapy.

The team will work together to generate human antibodies targeting ALK. They will test the antibodies in vitro to select the best candidate(s) to take forward for testing in an animal (mouse) model.

What difference will this project make?

High-risk neuroblastoma is treated with a remarkably intensive regime including extensive surgery, high-dose chemotherapy, radiotherapy, stem cell transplantation and anti-GD2 immunotherapy. Despite this aggressive approach, which results in major long term toxicities, the survival rate is poor.

New treatment approaches with reduced toxicity are desperately needed and this work by Professor Anderson and colleagues has a real chance of developing an effective therapy with little long-term toxicity.

If their work is successful, the next step will be to translate the work into an early phase clinical trial for high-risk neuroblastoma patients.  

* this project is being funded in collaboration with Great Ormond Street Hospital Children’s Charity, with each charity contributing 50 per cent of the total cost of £302,390.

Read more: About neuroblastoma


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