The Power of Collaboration to Find a Cure…
The Results of Prof Juliet Gray’s Research Into Antibody Immunotherapy for Children with Neuroblastoma.
Prof Juliet Gray (L) and Dr Tia Kulanthaivadivel (R)
In 2019, Neuroblastoma UK joined forces with childhood cancer charities The Bradley Lowery Foundation and Niamh's Next Step to support more vital research into neuroblastoma.
Together, the three charities funded essential 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. This was led by Prof Juliet Gray, with Prof Stephen Beers as Co-Investigator, and Dr Tia Kulanthaivadivel, at the Centre of Cancer Immunology at the University of Southampton, and in collaboration with Dr Alexander Davies and Dr Simon Rinaldi from the Department of Clinical Neurosciences at the University of Oxford.
The project’s purpose was to improve our understanding of how anti-GD2 antibodies work and how they cause pain, and to design an anti-GD2 antibody that would be more effective in killing the neuroblastoma cells and less toxic than those currently used. It also aimed to investigate if anti-GD2 therapy could 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.
The hope was that, if successful, this project could lead to the development of a clinical antibody for trial in children which would result in less pain and neurotoxicity and also improve the efficacy of anti-GD2 therapy, ultimately curing more children.
How collaboration leads to hope…
Nearly five years on, the research has shown that even anti-GD2 antibodies which could not interact with the immune system at all, were still able to slow the growth and interaction of neuroblastoma cells. In preclinical tumour models, findings suggest that different antibodies resulted in varying degrees of pain and other side effects. Surprisingly, the researchers discovered that antibodies which could not activate
complement still caused significant side effects, while other antibodies, which had other immune functions disrupted, had far fewer side effects. Encouragingly, the antibody which resulted in the least side effects was still effective at slowing tumour growth.
This study has been successful in demonstrating the complex issue of the mechanism of action of anti-GD2 antibodies. The results challenge the belief that immune cells and macrophages are essential for the therapeutic function of anti-GD2 and that pain is dependent on complement activation.
Data from this project supports further work to develop antibodies with fewer side effects and will be used as a basis for further research in the hope of developing more effective, but less toxic, treatments for children with neuroblastoma.
