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Reducing toxicity in treatment for children with high-risk neuroblastoma

Neuroblastoma is one of the most common childhood tumours, and in its high-risk form is one of the most difficult childhood cancers to cure, despite intensive therapy. This important project is researching a new immunotherapy approach to develop more effective and less toxic treatments to give more children a chance of survival.

New approaches to treating high-risk neuroblastoma in children are desperately needed, as current treatments are highly toxic and not always effective. With this work Professor John and his team have a real chance of developing an effective immunotherapy approach.

* 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.

Project Progress...

John Anderson who is researching ways to reduce the toxicity of neuroblastoma & osteosarcoma treatment

Project Details

  • Project Title

    Combinatorial targeting of Anaplastic Lymphoma Kinase (ALK) for neuroblastoma immunotherapy

  • Lead Researcher

    Professor John Anderson

  • Research Centre

    Institute of Child Health, University College London

  • City & Institution Postcode

    London WC1N 1EH

  • Start Date

    2 January 2013

  • Duration

    4 years 2 months

  • Grant Amount

    £151,195

Overview

Neuroblastoma – a nerve tumour – is one of the most common childhood cancers, with around 100 children, mostly under five years old, diagnosed every year in the UK.

Around 40 per cent of them have a high-risk form that is essentially incurable using conventional treatments (chemotherapy, radiotherapy, surgery). Although these treatments are currently all that we can give them, they also have side effects including infertility, kidney and hearing impairment and increased risk of second cancers.

Immunotherapy, which attempts to stimulate the body’s immune system to reject and destroy tumours, are successfully treating several cancers.

Immunotherapy for treating childhood cancers is very new, but a recent clinical trial has shown some success with neuroblastoma, increasing survival by 15 per cent in high risk patients. It targets a protein called GD2 found on the surface of neuroblastoma cells. But it’s not ideal, since GD2 is also present in normal cells and tissues.

The research team is aiming to make immunotherapy for neuroblastoma more effective, and reduce its toxicity.

What difference will this project make?

New treatment approaches for high-risk neuroblastoma with reduced toxicity are desperately needed, and this work by Professor John and his team has a real chance of developing an effective therapy with little long-term toxicity.

They’ll target a newly identified protein molecule called ALK. ALK is present on the surface of neuroblastoma cells from most children with the disease. Importantly, however, it’s absent from normal cells, meaning that targeting ALK wouldn’t result in the same toxicity as anti-GD2 therapy.

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

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.

About the Research Team

Professor John Anderson, a paediatric oncologist at Great Ormond Street Hospital (GOSH), is one of the UK’s leading experts on neuroblastoma, both in the laboratory and in a clinical setting. He’ll work with colleagues Dr Martin Pule and Dr Karin Straatfhof from UCL Institute of Child Health, Professor Louis Chesler, from Institute of Cancer Research; and Professor Kerry Chester, from UCL Cancer Institute.

His colleagues on this project all bring crucial expertise in different aspects of the project, combining international expertise in antibody technology, neuroblastoma modelling, and paediatric translational immunotherapy.

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