Promising early results in CAR T-cell trial for common childhood cancer

Results from a phase I clinical trial Involving the UCL Great Ormond Street Institute of Child Health (ICH) show that CAR T-cell therapy could achieve activity against neuroblastoma tumours, opening the door to progress this approach towards further clinical trials.

In the study, published in Science Translational Medicine, researchers at the ICH and the UCL Cancer Institute modified the patient’s own T-cells to equip them to recognise and kill neuroblastoma tumour cells. Patients with relapsed or refractory (where the disease does not respond to treatment) neuroblastoma were treated on this Cancer Research UK-funded study, which is one of the first to show the ability of CAR T-cells to induce anti-tumour activity in a solid (non-blood) cancer.

Neuroblastoma is one of the most common types of cancer in children, with up to 100 children in the UK diagnosed each year. Half of patients diagnosed have so-called ‘high risk’ disease due to their age, tumour biology or spread of the disease. Treatment for this patient group is highly intensive but - despite this - in up to half of the patients still not effective and the cancer returns.

Tumour cells can often stay hidden from a patient’s immune system, so researchers have developed a highly specialised form of cancer treatment using a patient’s own modified T-cells. These cells are equipped with a Chimeric Antigen Receptor – or CAR – that means the engineered T-cells can now recognise and kill tumour cells.

In this new study, the CAR T-cells were modified to recognise a molecule called GD2 that is highly expressed on virtually all neuroblastomas. This molecule is not commonly found in large amounts on healthy tissues which makes it an ideal target for this type of treatment.

The researchers found that, when treated with a sufficient dose of modified cells, the CAR T-cells were activated and could induce rapid reduction in tumour in some of the patients treated. Importantly, the CAR T-cells did not cause any harmful side effects in healthy tissues that express the GD2 molecule.

Dr Karin Straathof, Consultant Paediatric Oncologist and research group leader at UCL Great Ormond Street Institute of Child Health, said:

The anti-tumour activity seen in this study was only transient, but it provides an important proof-of-principle that CAR T-cells directed at the GD2 molecule could be used against solid cancers in children. The research team will now look at how they can modify their approach to produce durable anti-tumour activity, and in collaboration with Autolus Ltd, are preparing for their next clinical study.