Vital Neuroblastoma projects we fund with your donations

​Collaborating to find a cure

​Earlier this year, Niamh’s Next Step joined forces with childhood cancer charities Neuroblastoma UK and The Bradley Lowery Foundation to fund more vital research into neuroblastoma.
 
Dr Juliet Gray is Associate Professor in Paediatric Oncology at the University of Southampton. Together, the three charities are funding her vital work into antibody immunotherapy for children with neuroblastoma, a form of treatment which relies on cells of the body’s own immune system to kill cancer cells.
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Dr Gray says “As lead investigator, I am working with my team on a clinical trial to understand and improve the effectiveness of anti-GD2 immunotherapy in neuroblastoma. The antibody acts against a sugar-fat molecule present on nearly all neuroblastoma cells called GD2 (disialoganglioside). When the antibody binds to GD2 on the neuroblastoma cells, the cells die in a different way than after chemotherapy or radiotherapy. This is called antibody dependent cytotoxicity.
 
“The introduction of immunotherapy with anti-GD2 antibody has seen improvements in the outcome of children with neuroblastoma and has become an international standard of care. However although early relapse rates are significantly reduced, long term benefits are less clear, suggesting that, in many children, relapse is delayed rather than prevented.
 
Furthermore, side effects from anti-GD2 are significant, with many children still developing severe pain and central nerve damage, such as paralysis. The majority of children with high risk neuroblastoma still die from their disease.
 
THE AIMS OF THE RESEARCH PROJECT
“The first aim of the project is to design a better anti-GD2 antibody that will be more effective in killing the neuroblastoma cells and less toxic than those which are currently used, to reduce the serious side effects of treatment.
 
If this project is successful, it would hopefully lead to the subsequent development of a clinical antibody, for trial in children. Ultimately it is hoped such an antibody would be result in less pain and neurotoxicity for children than current antibodies, and also help cure more children. 
 
...If this project is successful, it would hopefully lead to the subsequent development of a clinical antibody, for trial in children with neuroblastoma…
“The project will also investigate if anti-GD2 therapy can be further improved by combining with two different agents (anti-PD-1 antibody and STING agonists) to stimulate the immune system and increase response to treatment.
 
Both of these agents are already in clinical trial, and therefore successful pre-clinical combinational strategies with anti-GD2 could be rapidly translated into clinical trial for children with neuroblastoma. Such trials would aim to improve the efficacy of anti-GD2 therapy, curing more children.
 
...Ultimately it is hoped such an antibody would be result in less pain and neurotoxicity for children than current antibodies, and also help cure more children with neuroblastoma…
“My motivation for research and new clinical trials comes from the patients that I see, and the need to find new and better treatments for the cancers that they have. New and different types of therapy are needed to improve survival rates for children with neuroblastoma. Anti-GD2 immunotherapy has already been shown to improve survival for these children, but there is still a lot of work to be done to improve survival rates further.
 
“Thanks to funding from Niamh’s Next Step, Neuroblastoma UK, and The Bradley Lowery Foundation, I hope the trials I am involved in can build on what has already been achieved, and deliver more effective immunotherapies.”

Funding research. Giving hope. 

Tony Heddon, Chair of Neuroblastoma UK says, “Thanks to our generous supporters, we have awarded nearly £7 million to UK research focusing on neuroblastoma. But more needs to be done. We rely on donations to continue to drive forward research into this terrible disease and give more families hope.”
 
Chris Curry, Niamh’s dad, Co-Founder and Chair of Niamh’s Next Step says, “Having collaborated on various neuroblastoma research projects over the last six years, we are very proud and excited to be working alongside Neuroblastoma UK and The Bradley Lowery Foundation to fund this project run by Dr Gray in Southampton. It’s amazing to continue funding vital projects like this in Niamh’s memory.”
 
Gemma Lowery, Bradley’s mum and founder of The Bradley Lowery Foundation says, “The Bradley Lowery Foundation believe collaborating with other like-minded charities and organisations is the best way to achieve the goals you desire. Working with so many great charities, we have been able to support vital research into neuroblastoma, in the hope that one day, it can be cured for good. BLF are honoured to join Neuroblastoma UK and Niamh’s Next Step in funding this research and we believe, together, great things can be achieved.’’

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Funding for SIOPEN, ( International Society of Paediatric Oncology Europe Neuroblastoma Group) supporting UK Neuroblastoma Clinical Research from 2014 to present day.... ​

​Niamh's Ne​xt Step are very pleased and proud to once again be joint funding the United 

Kingdom's annual levy to the European research network that carries out research into Neuroblastoma, the International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN).  Along with Neuroblastoma UK, The Thomas Ball Children s Cancer Fund, The Henry Allen Trust, Smile with Siddy and Solving Kids Cancer. 

This funding means that UK children will continue to have access to clinical Neuroblastoma trials and will also ensure that there is continued maintenance and development of the SIOPEN database, where all data on trials from the European countries involved in the High Risk Neuroblastoma study, is collated, analysed and used accordingly for the benefit of UK children with Neuroblastoma.

Thank you to everyone who has supported and donated as without your generosity this project would not be possible. 

You can read more about this project at: http://www.siopen.org/about/member-countries-centres/23-countries/65-united-kingdom

Neuroblastoma Research Funding
collaboration with Sparks and Great Ormond Street Children's Hospital

From 8th of September 2016 this vital reserach project will run for 18 months until the 7th of March 2018
and is being carried out by Prof Auturo Sala at UCHL, London and Brunel University, London.

Background
Neuroblastoma is one of the most common types of cancer seen in childhood with around 100 new cases diagnosed each year.  The severity of the disease can vary greatly. In about 20% of neuroblastoma tumours there is a change in a gene called MYCN.  This is known to make the tumour more aggressive as it causes it to grow rapidly. Children with this type of neuroblastoma undergo a gruelling course of chemotherapy, surgery and radiotherapy, yet still the prognosis is very poor.  More effective therapies are desperately needed.

The Project
In this study Prof Sala and his team will investigate whether a type of stem cell that has been engineered to carry a cancer-killer gene can be used to find and eliminate neuroblastoma cells in patients.  These cells are already being manufactured for a large clinical trial in adult lung cancer to assess whether they can find and clear tumour cells.
In this study, Prof Sala and his team will also extend this work by assessing whether the modified stem cells can clear tumours in mice transplanted with human neuroblastoma cells taken from patients.
Impact
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The advantage of using this stem cell-based therapy over some other approaches is that all neuroblastoma cells should be killed, independently of their genetic makeup (tumours are made up of cells with different active genes making them harder to kill). If the team validate the effectiveness of the modified stem cells in mouse models of neuroblastoma, a clinical trial could be established very quickly.

​Institute of cancer research at Newcastle University 

There is a desperate need to develop new treatments for children with high-risk neuroblastoma. Chemotherapies currently used act by damaging the genetic material of cells, and this starts a sequence of events that tell the cancer cells to die, shrinking tumours and treating the cancer. Although chemotherapies are effective, they are not selective for cancer cells and can damage and kill normal healthy cells of the body. 

Courtesy of Newcastle University

Professor Tweddle and her colleagues are looking at new ways to kill cancer cells whilst minimising the unwanted effects on normal cells with the aim of developing new cancer therapies for children with neuroblastoma.

New drugs which target the genetic mistakes in neuroblastoma, so-called targeted therapies, which are not present in normal tissues, are less likely to have the short-term and long-term side-effects associated with chemotherapy and radiotherapy. 

When used in combination they are also less likely to lead to the tumour becoming resistant to their effects.

We have been studying a new class of targeted drugs called MDM2-p53 inhibitors in neuroblastoma. MDM2-p53 inhibitors work by preventing p53 (a protein which suppresses cancer) binding to a protein which destroys p53 called MDM2, to keep p53 levels high in the cell and cause the cell to die.

Neuroblastoma is an excellent tumour in which to test MDM2-p53 inhibitors as p53 is essentially normal and not mutated. We propose that combining MDM2-p53 inhibitors with other novel targeted therapies which work on different pathways affected by genetic mistakes in neuroblastoma, will lead to a greater degree of cancer cell killing. Combinations of targeted agents which are best at killing neuroblastoma cells in these laboratory studies will then hopefully be taken forward to clinical trials in the future.

We are enormously grateful to Niamh's Next Step and the Neuroblastoma Society for funding our work, which we look forward to commencing in early 2015 and which will run for two years. 

You will be able to read how things are going for Professor Tweddle and the team by reading their blog once the research has started.

Professor Deborah Tweddle 
Professor of Paediatric Oncology at The Institute of Cancer Research at Newcastle University, UK