Born in June 2014, Layla was a happy and healthy baby. She weighed 7lb 10 – well within the parameters for newborns carried to full term – but, at three weeks old, Layla's health started to turn. She struggled to eat and cried constantly. Her heartbeat raced at an irregular and worrying pace and what was thought to be a stomach bug was revealed to be Infant Acute Lymphoblastic Leukaemia (ALL).
At just 14 weeks old, Layla was taken to Great Ormond Street Hospital (GOSH) for intensive and immediate treatment, undergoing several rounds of chemotherapy and a bone marrow transplant to replace her damaged blood cells. Yet, after several weeks of aggressive treatment, the cancer returned. With no signs the first round of treatment had worked it was determined a second course of chemotherapy wouldn’t be viable.
Still shy of her first birthday, Layla was recommended palliative care. Her parents refused.
In a statement from Great Ormond Street Hospital, Layla's mother, Lisa, recalls: "We didn’t want to accept palliative care and give up on our daughter... so we asked the doctors to try anything." So they turned to a radical new immunotherapy treatment that had shown promise in fighting blood cancers - one that had only previously been tested in mice.
Waseem Qasim is a Professor of Cell and Gene Therapy at University College London Institute of Child Health. He is also a Consultant Immunologist at Great Ormond Street Hospital and an NIHR Research Professor. In 2015, he and his colleagues were in the process of creating an "off-the-shelf" bank of modified blood cells. His work had been largely experimental, utilising TALEN and CRISPR molecular tools in order to edit the orchestrators of our immune response - engineering T cells to be powerful "anti-leukaemic soldiers."
The cells are engineered ex-vivo, during a 19-day procedure. Blood cells are collected from a healthy donor and placed in sterile bags to "grow" before they are activated with antibodies to enact mitosis. This is a process of cellular division that results in two "daughter" cells.
From here, extra genes are added to the cells - a process compounded by electroporation in which a rush of electricity increases the permeability of the cell membrane, allowing new DNA to be introduced directly into the cell. The cells are then cleaned and processed in a bioreactor.
This treatment technique can yield up to 50 million frozen cells - known as UCART19 - all of which are suitable for universal donation.
– Read all of our WIRED Health 2017 coverage.
The CAR-T cell adaption is two-fold. Precise enzymes are guided to sites in the genome where they create double strands – as this is repaired, it knocks out the function of that gene. Without their natural immunity, the T cells are effectively invisible to the powerful leukaemia drugs that would usually devastate them. By introducing new receptors into their cell surface, T cells are able to turn their function from defence to offence - recognising early stages of leukaemia and releasing chemicals to kill tumour cells before they develop.
In Layla's case, only a single 1ml vial of UCART19 cells was available and its use could only be granted by obtaining permission from an emergency ethics committee. There was no precedent; no human had ever tested it before and the risks were untold. However, so was the possibility of its success.
“We only really had modelling and animal testing,” Professor Waseem Qasim told WIRED Health 2017. Normally, a drug would go through copious clinical tests to ensure its safety for human usage - but Layla had “run out of options.”
One thing was certain. In order to treat Layla, doctors would have to completely delete her immune system and build it again from the ground up. The new cells would have to reconstitute and recover the whole system. Read more: The secret to curing cancer could lie in treatments that 'supercharge' immune systems
After obtaining a special authority licence, Qasim was able to use the UCART19 cells to treat Layla. She was given a combination of Lymphodepleting chemotherapy and anti-CD52 serotherapy, followed by a single-dose infusion of UCART19 cells. An intravenous line fed the cells directly into her body, in a procedure taking roughly 10 minutes. Afterwards, she spent several months in isolation to protect her from contracting any infections while her immune system was so weakened.
The results were profoundly hopeful.
"There were very efficient genetic changes," Qasim noted. The T cells were actively targeting the cancer. As Qasim describes: "A single cell can kill one after another after another."
Doctors watched as the rates of cancer cells began to fall and 28 days after the initial injection of UCART19 cells, Layla was in molecular remission.
Now, close to 18 months after Layla's treatment, Professor Qasim is able to demonstrate the fruit of his work at the Royal College of Surgeons in London. In both Layla's bone marrow and in her peripheral systems, the measurements are still the same - with no remaining trace of cancer.
“The disease disappears and doesn’t come back,” Qasim says.
Currently Professor Qasim's work is in the translational phase of development, and is yet to be granted a full license. A formal phase 1 trial of the treatment is expected to begin over the next 12 to 18 months and will focus on children with similar types of leukaemia at Kings College Hospital, London.
While this is still too early to be treated as a cure, Layla is one of the first lives to directly benefit from genetic engineering. Her story is a powerful symbol of the need for further exploration into the relationship between technology and medicine - and the possibilities that can be engineered from hopeless situations.
This article was originally published by WIRED UK
