Cellectis wows with successful CAR T treatment for leukaemia

Cellectis took a huge step forward in treating leukaemia after producing astonishing results in one gravely ill 11-month-old baby girl.

The French biotech firm is one of a number of companies developing CAR-T immunotherapy treatments, but has taken a surprise lead with this exceptional, one-off use of UCART19, its first ever use in humans.

The baby girl Layla had an incurable, refractory and highly aggressive acute lymphoblastic leukaemia (ALL), and was given the treatment as a 'last chance' compassionate use protocol with the consent of her parents.

The work was carried out by pioneering research teams at London's Great Ormond Street Hospital (GOSH) in conjunction with UCL Institute of Child Health's (ICH) – who reported astonishing results late last week.

Layla had not responded to chemotherapy, and had no other option but palliative care. Now, two months on from her single treatment, Layla is free of cancer and doing well.

The treatment consisted of 1ml of UCART19 cells delivered via intravenous line in around 10 minutes. After the cells had been delivered, Layla spent several months in isolation to protect her from infections while her immune system remained extremely weak.

Clinicians were surprised by how few side effects Layla experienced. She did require a second bone marrow transplant, but was able to leave hospital one month after this procedure.

Professor Waseem Qasim, Professor of Cell and Gene Therapy at UCL ICH and Consultant Immunologist at GOSH, explained: "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."

Many drug developers had been sceptical that Cellectis' therapy could bypass some of the technical challenges facing other CAR-T therapies.

Rivals Novartis, Kite, and Juno are all developing CAR-T therapies which require a complicated and expensive process of personalising the treatment for each individual patient. In contrast, Cellectis' UCART19 is derived from 'off-the-shelf' CAR-Ts, which can be used in any patient.

The UCART19 production process relies on another cutting-edge technology, the gene-editing technique known as TALEN. This molecular procedure acts like very accurate scissors, cutting specific genes 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.

If the treatment can show similar success in full-scale trials, it will have a huge advantage over its competitors. The firm saw a huge rise in its share price in response to the news, and plans to present more data on UCART19 and its other lead candidate UCART123 (being developed for acute myeloid leukaemia) at the American Society of Haematology conference next month.

"Cellectis' main objective is to provide cancer patients with accessible, cost-effective, off-the-shelf allogeneic CAR-T therapies across all geographies. With clinical trials for the first gene-edited UCART on the horizon, it could be the beginning of a revolution in cancer immunotherapy," said Dr André Choulika, chairman and chief executive of Cellectis.

However, as these results are in just one patient, and just two months after treatment, caution is being urged.

Cellectis now plans to begin full-scale clinical trials of UCART19 cells in early 2016.

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