Child’s life saved from leukemia in ground-breaking use of gene-edited immune system cells

Doctors at Great Ormond Street Hospital (GOSH) successfully used “off the shelf” genetically engineered white blood cells (T-cells) in a last ditch effort to treat a one-year old girl, called Layla, who was suffering from acute lymphoblastic leukemia (ALL) that had resisted chemotherapy. This is the world’s first instance of this targeted cancer therapy in a human patient.

To achieve this GOSH doctors worked with research scientists at University College London’s (UCL) Institute of Child Health (ICH) and biotech company Cellectis. The gene-edited T-cells were modified using a “molecular toolkit” that scientists have pirated from a few genes found in certain bacteria – especially a biological editing tool called TALEN.
TALEN is a combination of a modular protein (TAL) that can effectively be “programmed” to find and bind very specific DNA sequences, together with an endonuclease (EN) which is a protein that can cut DNA, ready to replace that gene with the version desired.

The modified T-cells are called UCART19 cells, and they are produced to fight leukemia in a two step process:
First, they have a gene that programs for a characteristic cell surface protein deleted – so the UCART19 cells will be “invisible” and remain safe from the anitibodies that are given to leukemia patients to destroy their existing, diseased immune system.
Secondly, the T-cells have the gene for the CAR19 surface protein added – CAR19 will bind the UCART19 cells to a different protein called CD19, which is only found on the surface of immature white cells (called “blasts” – lymphoblasts in ALL) that proliferate in leukemia and “crowd out” other healthy blood cells, thus causing the disease symptoms. Once bound to the leukemia cells (lymphoblasts) the UCART19 cells recognise them as foreign and destroy them.

nci-vol-4345-72LeukemiaPubDomCredNCIAlanHooofringColourInvert
(Above: The blood stream of a healthy subject vs. a leukemia patient.
RBCs = Red Blood Cells. WBCs = White Blood Cells.

Public domain image, credit: NCI, Alan Hoofring.
Modified by J.Overton)

Clinical trials taking place at the moment normally begin with white blood cells taken from the patient because these run least risk of causing auto-immune problems, but this “bespoke” method of production is expensive. However, due to the chemotherapy and highly agressive nature of the leukemia she suffered, little Layla did not have enough white blood cells left to work with, so the team gave her “off the shelf” UCART19 cells created from donated T-cells.

Previously, this experimental treatment had only been tested on mice in the lab, in fact it was so new that GOSH had to convene an emergency ethics meeting to decide whether Layla should receive it. As routine chemotherapy and a bone marrow transplant had already failed to help Layla, and her condition was worsening, all the doctors had left to offer was either palliative care to relieve her suffering during terminal illness, or the hope of possible recovery with the UCART19 cells. So, together with Layla’s parents, they decided to opt for treatment.

After about two weeks of receiving the UCART19 cells, Layla got a rash which is characteristic of the expected immune response, and a few weeks later results showed her system was clear of leukemia cells. After two months Layla received a second bone marrow transplant, which was successful, and once her healthy blood cell count was high enough she was able to return home with her family to recuperate further. While it is still too early to declare Layla cured, and she is still being monitored in case the leukemia returns, so far she is doing well.

Hopefully, further trials will show similar success and this targeted treatment may then become more widely available for other leukemia sufferers.

(Clinical information from GOSH Press Release, biotechnology information from New Scientist  and The Tech Museum of Innovation)

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