Doctors at London's Great Ormond Street Hospital have used genome editing to successfully treat two children with leukaemia.
The initial results were widely reported in the media in November 2015 (see BioNews 827), and the two case studies have now been published in the journal Science Translational Medicine. Both children showed complete remission of the disease within 28 days and were free of cancerous cells one year after receiving the treatment.
Layla Richards was the first child to receive the experimental cell-based treatment in June 2015. She was three months old when she was diagnosed with B-cell acute lymphoblastic leukaemia (B-ALL) and had previously undergone chemotherapy and a bone-marrow transplant. But these failed, and the leukaemia returned. She received the experimental treatment when she was one year old. The London team then repeated the procedure on a second baby girl, aged 16 months and with a similar medical history to Layla, in December 2015.
The treatment was based on an existing system – CAR T-cell therapy – which uses a patients own T cells and genetically modifies them to target cancerous cells. But it is hard to collect enough healthy T cells from leukaemia patients.
Professor Waseem Qasim at University College London, who led the study, created a universal CAR T-cell therapy using T cells taken from a healthy person, overcoming the need to fine-tune the infants' own immune cells. They used the genome editing tool TALENs – transcription activator-like effector nucleases – to silence the gene that would cause the T cells to be rejected.
'The patient could be treated immediately, as opposed to taking cells from a patient and manufacturing them,' said Dr Julianne Smith, vice-president of CAR-T development for Cellectis, the New York biotech company that manufactures the cell treatment.
'In the off-the-shelf approach, blood is collected from a donor and then turned into hundreds of doses that can then be stored frozen,' said Dr Smith. 'We estimate the cost to manufacture a dose would be about $4000,' she added. The cost of the personalised therapy using a patient's own cells is around $50,000.
The results have been challenged by some researchers, who have pointed out the children received standard chemotherapy on top of the cell-based therapy. 'There is a hint of efficacy but no proof,' noted Professor Stephan Grupp, director of cancer immunotherapy at the Children's Hospital of Philadelphia, Pennsylvania. 'It would be great if it works, but that just hasn't been shown yet.'