Dr Karin Straathof, UCL Institute of Child Health, London
Less than half of children with an aggressive form of the childhood cancer neuroblastoma can be cured, even with the most intensive treatment. Dr Karin Straathof is developing a new immunotherapy approach to target this disease. Not only should this provide a new treatment option for children who can’t currently be cured but, importantly, it should be less toxic than existing treatments.
Amount of grant: £251,392 | Date of award: July 2016
Neuroblastoma is a childhood cancer that often returns, despite intensive combination treatment with chemotherapy, radiotherapy and surgery. Relapsed neuroblastoma is difficult to treat and has a poor outlook.
In addition to the relapse risk, current treatment causes significant side-effects both during treatment and in the longer term, for those who survive. This highlights the urgent need to develop new treatment strategies that will not only increase the cure rate but also reduce toxicity.
A promising new treatment approach is immunotherapy using T-cells, important cells of our immune system. The role of T-cells is to kill abnormal cells such as cells that are infected by viruses. They can also destroy cancer cells. Cancer cells often evade immune detection, however, because they are recognised as ‘self’ and don’t have a ‘tumour identifier’ that will attract the attention of T-cells.
In this project, Dr Straathof is using proteins called antibodies to mark the tumour cells for destruction.
In the normal course of events, antibodies are produced by other immune cells and bind with infected or ‘bad’ cells to mark them for destruction by T-cells.
A special class of artificial antibody called ‘Bi-specific T-cell Engagers’ (‘BiTEs’) has been designed to act as a tumour identifier. BiTEs act as ‘binding bodies’, bringing together the patient’s T-cells and the tumour cells and so facilitating the killing of the tumour cells.
The use of BiTEs has shown great promise in the treatment of leukaemia. The development of BiTEs for leukaemia treatment has provided important insights in optimal BiTE design; the team will now take advantage of this knowledge to predict which type of BiTE will work best for neuroblastoma.
Building on this knowledge, the team will conduct careful testing of a panel of BiTEs to identify one that is highly effective at facilitating the destruction of neuroblastoma tumour cells by the patient’s own T-cells.
Their second challenge is to work out how best to incorporate BiTEs into the current, complex treatment schedule for neuroblastoma which already includes surgery, radiotherapy and several phases of chemotherapy.
About the research team
This research team brings together investigators with unique expertise in design and development of immune cell-based treatments to develop the next generation of immunotherapy for neuroblastoma.
Dr Karin Straathof is a Wellcome Trust Fellow at the UCL Great Ormond Street Institute of Child Health, with more than 15 years’ experience in the development of cellular and immune treatments for cancer.
She is working with colleagues Dr Martin Pule - an expert in the design of BiTEs and other T-cell immunotherapies – and Professor John Anderson - a clinician-academic paediatric oncologist who leads immunotherapy for solid cancers at Great Ormond Street Hospital.
Professor Anderson is the lead investigator of a study of T-cells reprogrammed to recognise and kill neuroblastoma tumour cells that opened in 2016. He treats a large number of children with neuroblastoma and has essential experience in the design of clinical studies and implementation of new treatment strategies into clinical care.
“The applicants are highly qualified and experienced to carry out the project. They are accepted in the international community as leading researchers in the field of immunotherapy of pediatric tumours,” external reviewer.
What difference will this project make?
Since currently less than half of children with aggressive neuroblastoma are cured - even with use of combination chemotherapy, surgery and radiotherapy - new approaches are desperately needed.
Treating cancer with immune cells recruited to the tumour using a ‘binding body’ or BiTE is a completely new type of therapy. As well as offering chance of cure to those who cannot be saved with existing treatment approaches, a further benefit is that it should have far less long-term toxicity.
With the information gained through this project, the team will be in a position to seek funding and approval to make BiTE therapy available to neuroblastoma patients in a clinical study. This could be achieved within the next five years.
If this method of developing BiTE treatment works well, the team will use the same strategy to develop BiTEs for other types of childhood cancer.
“Even with the use of multi-modal therapy (chemotherapy, surgery, stem cell transplantation, radiation and immune modulation), the current long-term survival rate for patients with high-risk neuroblastoma is ~50 per cent. This grant is building upon the success seen with BiTE therapy for the treatment of relapsed/refractory leukemia to design an off-the-shelf BiTE for neuroblastoma and potentially other solid tumours. While there are many international labs working on BiTE technology, if successful, this would be one of the first translational studies targeting solid tumours and more specifically, a pediatric solid tumour.”
Karin Straathof spoke to ecancertv at our recent conference about developing novel treatments for paediatric neuroblastoma:
Read more: About neuroblastoma | Other neuroblastoma projects | Other immunotherapy projects