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Engineering immune cells for the optimal eradication of neuroblastoma

Neuroblastoma is one of the most common solid tumours to occur in children. It can be exceptionally difficult to treat and, despite intensive treatment, around one third of patients cannot currently be cured. In this project, Dr Gilham is harnessing the power of the immune system by engineering specific immune cells to destroy tumour cells. He will lay the essential groundwork in the laboratory to enable progression to clinical trial in children.

Project Progess...

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Project Details

  • Project Title

    The genetics of familial leukaemia

  • Lead Researcher

    Dr David Gilham

  • Research Centre

    Paterson Institute for Cancer Research

  • City & Institution Postcode

    Manchester, M20

  • Start Date

    29 March 2013

  • Duration

    4 years

  • Grant Amount

    £183,706

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Information about neuroblastoma

Neuroblastoma

Neuroblastoma is the second most common solid tumour in childhood, affecting just under 100 children a year in ...

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Overview

Neuroblastoma is one of the most common solid tumours to occur in children, predominantly affecting children under the age of five years.

Around 40% of children diagnosed with neuroblastoma have a high-risk form that is essentially incurable using conventional treatments (chemotherapy, radiotherapy, surgery).

Immunotherapy approaches, turning the power of the immune system against the tumour, have already shown considerable promise in the treatment of neuroblastoma.

The 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.

Gene therapy has been used to modify T cells, adding proteins called T cell receptors that can overcome some of these tumour defence systems. Early phase clinical studies of this T cell therapy have shown promise but, on their own, these T cell receptors lack the ability to fully activate the T cell.

In this project, Dr Gilham and colleagues will generate and test additional proteins, called “chimeric antigen receptors” (“CAR”), that can fully activate T cells thereby enhancing their anti-tumour potential.

What difference will this project make?

The obvious benefit of this work is the potential to improve survival in children with neuroblastoma. If the technology functions optimally, it is strongly possible that the T cells may fight the local tumour and then provide a long-lived population of cells that could potentially fight recurring tumour cells at later times, thus guarding against relapse.

Neuroblastoma

About the Research Team

The research team incorporates scientists and clinicians with strong interests in the immune therapy of 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 the research group and the infrastructure to deliver these new therapies. They are working with Dr Guy Makin, the national lead for phase II neuroblastoma clinical trials, ideally placing them to bring new therapies rapidly to the clinic for the benefit of children with poor prognosis neuroblastoma.

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