A novel CAR T-cell therapy that is designed to target cancerous tumours has shown promising early results in children with neuroblastoma, according to a new study.
It is one of the first studies to demonstrate that CAR T-cells achieve rapid regression against a solid cancer and although the beneficial effects lasted for a short time, it provides important evidence that this specific CAR T-cell treatment could be used as a future treatment for children with solid cancers.
For this phase I clinical trial, researchers at the UCL Great Ormond Street Institute for Child Health (GOS ICH) and the UCL Cancer Institute, UK, modified the T-cells of 12 children with relapsed or refractory neuroblastoma so that they could recognise and kill the tumour cells.
The research, published in Science Translational Medicine, is one of the first studies to demonstrate CAR T-cells achieving rapid regression against a solid cancer (non-blood cancer).
Although the beneficial effects only lasted a short time, the study provides important evidence that this specific CAR T-cell treatment could be used as a future treatment for children with solid cancers.
Existing treatment for children with an aggressive type of neuroblastoma includes surgical removal, chemotherapy with stem-cell transplant, radiotherapy and antibody therapy, but long-term survival is between 50% and 50%.
For this study, the patients’ own T-cells were modified with a CAR to target the GD2 surface protein, which is highly abundant on almost all neuroblastoma cells, but found at very low levels in healthy cells.
Researchers found that when using a sufficient dose – a minimal cell dose of 108/m2 – of the modified CAR T-cells, it induced rapid reduction in tumour size in some of the patients.
These effects were short lived but the CAR T-cells did not cause any harmful side effects in healthy tissues that express the GD2 molecule.
Lead author Dr Karin Straathof, research group leader at UCL GOS ICH and consultant paediatric oncologist at Great Ormond Street Hospital NHS Trust said: “It’s encouraging to see the anti-tumour activity induced by these modified T-cells in some of the patients on this study.
“While the anti-tumour activity seen was only transient, it provides an important proof-of-principle that CAR T-cells directed at the GD2 molecule could be used against solid cancers in children.
“New treatments are needed for high-risk neuroblastoma and with more research we hope to develop this further into a treatment that results in lasting responses and increases the number of patients that can be cured.”
Senior author, Dr Martin Pule of UCL Cancer Institute, added: “Targeting of solid cancers by CAR T-cells is dependent on their infiltration and expansion within the tumour microenvironment, and thus far fewer clinical responses have been reported.
“The rapid regression in neuroblastoma cells is promising, particularly as this activity was observed in the absence of neurotoxicity which occurs with antibody-based approaches that target GD2.
“Targeting neuroblastoma with GD2 CAR T-cells appears to be a valid and safe strategy but requires further modification to promote CAR T-cell longevity.”
For the next clinical study, the research team is to look at how they can modify their approach to produce durable anti-tumour activity.
Straathof K, Pule M, Anderson J. Antitumor activity without on-target off-tumor toxicity of GD2-Chimeric Antigen Receptor T cells in patients with neuroblastoma. Science Translational Medicine 25 November 2020; doi: 10.1126/scitranslmed.abd6169
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