High-risk neuroblastoma is currently incurable, and we urgently need a new approach. Immunotherapy is showing promise as a way to kill cancer cells, so we’re funding this project to help find a way to enable children’s own immune systems to fight back.
Dr David and his team are working on a way to modify cells in the body’s own immune system so they can target and kill cancer cells – a possible cure for an incurable childhood cancer.
Enhancing immunity against neuroblastoma through the exploitation of antigen-specific T cell co-stimulation receptors
Dr David Gilham
University of Manchester
Manchester, M20 4BX
5 November 2013
Neuroblastoma is one of the most common solid tumours to occur in children, mostly affecting children under the age of five. Around 40% of them have a high-risk form that is essentially incurable using conventional treatments (chemotherapy, radiotherapy, surgery). So we’re urgently looking for new and better types of treatment
Immunotherapy approaches, turning the power of the immune system against the tumour, have already shown considerable promise as treatments for neuroblastoma.
Our immune system consists of a variety of different cells that protect us against pathogens like bacteria and viruses. Certain immune cells called T cells have the potential to kill tumour cells, but unfortunately tumours have an armoury of mechanisms that enable them to avoid recognition and eradication. So Dr David and his team are looking for a way to beat them.
This project has the potential to find treatments that will help more children affected by neuroblastoma to survive. They should also have fewer side-effects than the currently available therapies, giving them a better chance of long-term recovery.
So far, gene therapy has been used to modify the T cells, adding proteins called T cell receptors that can overcome some of the tumour defence systems. Early phase clinical studies of this T cell therapy have shown promise but, on their own, these receptors can’t fully activate the T cell.
In this project, Dr David and colleagues will generate and test additional proteins, called chimeric antigen receptors (CAR) that can fully activate T cells, making them better and stronger as potential anti-tumour weapons.
If the technology that Dr David and his team are developing works as they expect it to, it’s strongly possible that the T cells could fight the local tumour and then provide a long-lived population of cells that potentially able to fight recurring tumour cells later. One of the biggest difficulties at the moment is the likelihood of tumours returning even after treatment. So this ability to keep killing the cancer cells even after the initial treatment would be a really important breakthrough in our ability to help these children live longer.
The research team incorporates scientists and clinicians with strong interests in devloping immune therapy for cancer and neuroblastoma.
Dr Gilham has worked for more than 15 years in the field of T cell therapy for cancer, and, along with his colleague Professor Robert Hawkins, has developed this research group and the infrastructure to deliver these new therapies.
They’re also working with Dr Guy Makin, the national lead for phase II neuroblastoma clinical trials, which means they’re in an ideal position to bring new therapies rapidly to the clinic for the benefit of children with poor prognosis neuroblastoma.