General Discussion

FourScore

(9,704 posts) Thu Nov 5, 2015, 11:14 PM Nov 2015

New "Gene Editing" Technique Clears Dying Baby of Leukemia

Thu Nov 05, 2015 at 06:11 PM PST
New "Gene Editing" Technique Clears Dying Baby of Leukemia
by Lib Dem FoP

Layla Foley was 14 weeks old when she was diagnosed as having an aggressive form of acute lymphoblastic leukaemia. Despite several rounds of chemotherapy and a bone marrow transplant, the cancer returned. Shortly before her first birthday her parents were advised to consider palliative end of life care. Then the doctors told them of an experimental treatment being developed at the hospital and they agreed to try it. Layla became the first patient worldwide to have a new form of "gene editing" treatment. After another bone marrow transplant, she is currently clear of cancer.

The treatment involves using “molecular scissors” to edit genes and create designer immune cells programmed to hunt out and kill drug-resistant leukaemia.

Only one vial of the treatment was available for Layla. An emergency ethics committee meeting was called to seek immediate approval for the treatment.

Layla’s father, Ashleigh Richards, 30, a driver, said: “It was scary to think that the treatment had never been used in a human before but, even with the risks, there was no doubt that we wanted to try the treatment. She was sick and in lots of pain so we had to do something.”

Layla was given a small 1ml infusion of genetically engineered cells, known as Ucart19 cells. She developed a rash, as doctors expected, but otherwise seemed well.

The doctors at the Great Ormond Street Hospital for Sick Children (GOSH) are cautiously optimistic this could provide a new and effective treatment for the most common cancer in children. It is also possible that it will be effective on a range of other drug-resistant cancers but this is only the very start of using the technique and will need to be shown to work long term.

Dr Paul Veys, from Great Ormond Street, said the transformation was one of the most remarkable things he'd seen in 20 years: "We're in a wonderful place compared to where we were five months ago, but that doesn't mean cure.

"The only way we will find out if this is a cure is by waiting that one or two years, but even having got this far from where we were is a major, major step."

He described the run of events as "almost like a miracle".

Layla's story is being presented at the American Society of Haematology, but this is only a single case that has not been tested in a clinical trial.

The team developing the technique came from GOSH, University College of London (UCL), UCL's Institute of Child Health and the French biotech company Cellectis. GOSH's press release explains in more detail.

The treatment works by adding new genes to healthy donor T-cells, which arm them against leukaemia. Using molecular tools (TALEN®) that act like very accurate scissors, specific genes are then cut in order to make the T-cells behave in two specific ways. Firstly, the cells became invisible to a powerful leukaemia drug that would usually kill them and secondly they are reprogrammed to only target and fight against leukaemia cells.

The team at GOSH and the UCL ICH, along with investigators at University College London and biotech company Cellectis, had been developing ‘off-the-shelf’ banks of these donor T-cells and the first of which was due to be used for final stage testing ahead of clinical trials. But, after hearing about this infant, the team received special permission to try the new treatment early.

Professor Waseem Qasim, Professor of Cell and Gene Therapy at UCL ICH and Consultant Immunologist at GOSH, explains: "The approach was looking incredibly successful in laboratory studies, and so when I heard there were no options left for treating this child’s disease, I thought ‘why don’t we use the new UCART19 cells?’

"The treatment was highly experimental and we had to get special permissions, but she appeared ideally suited for this type of approach."

The patient’s parents were also keen to try the treatment. Mum, Lisa, says: "We didn’t want to accept palliative care and so we asked the doctors to try anything for our daughter, even if it hadn’t been tried before."

The treatment consisted of 1ml of UCART19 cells delivered via intravenous line in around 10 minutes. After the cells had been delivered, the patient spent several months in isolation to protect her from infections while her immune system was extremely weak. Throughout this time, the patient stayed generally well.

After several weeks there were signs that the treatment was working. Professor Paul Veys, Director of bone marrow transplant at GOSH and the patient’s lead clinician, says: "As this was the first time that the treatment had been used, we didn’t know if or when it would work and so we were over the moon when it did. Her leukaemia was so aggressive that such a response is almost a miracle."

Once doctors were confident that the leukaemia cells had been removed, the patient was given a bone marrow transplant to replace her entire blood and immune system which had been wiped out by the treatment. The child is now recovering well at home, although she returns to GOSH regularly to check that her bone marrow cells are healthy and blood counts continuing to normalise.

Full clinical trials funded by Cellectis are now being planned to test UCART19 cells in larger groups of patients and are set to begin early in 2016. In light of the recent bad news about price hikes for generic drugs, the statement by the company is particularly interesting:

“Cellectis main objective is to provide cancer patients with an accessible, cost-effective, off-the-shelf allogeneic CAR-T therapies across all geographies. With clinical trial for the first gene-edited UCART on the horizon, it could be the beginning of a revolution in cancer immunotherapy,” says Dr. André Choulika, Chairman and CEO of Cellectis.

GOSH is one of the world's leading centers for the treatment of children. You may recognize the name from the 2012 London Olympics opening ceremony where patients and staff from GOSH joined other NHS workers in celebrating universal health care and children's literature. As well as British NHS patients, it takes children from all over the world, often funded by their home governments. Part of its charity collecting is used to build hotel type accommodation so parents can stay far from home while their children receive treatment. UCL and UCLICH are of course also government funded institutions and, working in cooperation with the French company, have developed this treatment.

The cost to Layla's parents of all her hospital treatment was of course nothing but in return for their courage in allowing the experimental treatment they have got back something priceless, Layla's life from her first birthday. Let's hope this will be a long one and that her pioneering treatment will save many more in the future.

http://www.dailykos.com/story/2015/11/06/1445433/-New-Gene-Editing-Technique-Clears-Dying-Baby-of-Leukemia