Gene-editing treatment successful in baby with advanced leukaemia

An experimental cell-based treatment using gene editing, previously only tested on mice, has successfully reversed advanced leukaemia in a one-year-old girl.

The girl is said to be free of cancerous cells but doctors say it is too soon to say whether she has been completely cured. Clinical trials are underway to test the treatment on other children.

Waseem Qasim, Professor of Cell and Gene Therapy at the Institute of Child Health in London, and the girl's immunologist, told the Guardian: 'This is a landmark in the use of new gene engineering technology, and the effects for this child have been staggering.'

The baby girl, Layla Richards, was three months old when she was diagnosed with a highly aggressive acute lymphoblastic leukaemia (ALL). She was treated with chemotherapy and a bone-marrow transplant but this failed to cure her.

The experimental treatment involved injecting genetically modified immune cells, called T cells, designed to specifically target cancerous cells. One month after the injection, all the cancerous cells had been killed. Details of the procedure are due to be presented at the American Society of Hematology in Orlando, Florida in December.

Previous gene therapies, which have had some success, have taken healthy T cells from the patient and genetically modified them to target cancerous cells before re-injecting them into the patient. But often patients do not have enough healthy T cells for this procedure. This new treatment uses immune cells from a healthy donor, so cells from the same donor can potentially be used for many different patients.

It also departs from conventional gene therapy in that gene editing not only allows new genes to be inserted in the cells, but also makes it possible to silence genes. The researchers used the gene-editing technology called TALENs, transcription activator-like effector nucleases, to remove genes that would cause the patient's immune system to reject the therapeutic T cells. They also deleted genes to prevent the cells from being destroyed by the strong immune-killing drugs given to leukaemia patients.

These 'off-the-shelf' T cells, called UCART19 cells, were produced by the New York biotech company Cellectis, but had only been tested on mice before. This is only the second time that gene-editing technology has been used in humans (see BioNews 764). 

Dr Simon Waddington, Reader in Gene Transfer Technology at University College London, who was not involved in the study, said: 'This report is exciting for two reasons. It describes the use of gene-editing technology ... to carefully and specifically modify existing genes – taking genetic medicine to a new level of precision.

'Secondly, the researchers have used this technology to create an off-the-shelf, generic cell therapy, rather than one specifically tailored for an individual patient. Therefore this could reduce the cost and complexity of the treatment, and ultimately bring benefit to a wider patient population.

'Nevertheless, this is a very early report and the researchers will now rigorously scrutinise the long-term safety and efficacy of the treatment, so more work has yet to be done before this is a technology available to all,' he cautioned.

The researchers hope that this technique could also be modified to treat other blood disorders and types of cancer.