A teenage girl’s incurable cancer was cleared from her body when a revolutionary new type of drug was first used.
All other treatments for Alyssa’s leukemia had failed.
So the doctors at Great Ormond Street Hospital used the “Basic Edition” to perform a feat of biological engineering to create a new living medicine for him.
Six months later, the cancer is undetectable, but Alyssa is still under surveillance in case it comes back.
Alyssa, 13, from Leicester, was diagnosed with T-cell acute lymphoblastic leukemia in May last year.
T-cells are meant to be the body’s guardians – seeking out and destroying threats – but for Alyssa, they had become the danger and were spiraling out of control.
Her cancer was aggressive. Chemotherapy and then a bone marrow transplant failed to rid her of her body.
Without experimental medicine, the only option left would have been to simply make Alyssa as comfortable as possible.
“Eventually, I would have died,” Alyssa said. Her mother, Kiona, said at this time last year that she dreaded Christmas, “thinking it was our last with her”. And then she “just cried” during her daughter’s 13th birthday in January.
What happened next would have been unthinkable just a few years ago and was made possible by incredible advances in genetics.
The Great Ormond Street team used a technology called Core Editing, which was invented just six years ago.
Basics are the language of life. The four basic types – adenine (A), cytosine (C), guanine (G) and thymine (T) – are the building blocks of our genetic code. Just as the letters of the alphabet spell out meaningful words, the billions of bases in our DNA spell out our body’s instruction manual.
Base editing allows scientists to zoom in on a specific part of the genetic code and then edit the molecular structure of a single base, converting it to another and modifying the genetic instructions.
The large team of doctors and scientists used this tool to design a new type of T cell capable of tracking down and killing Alyssa’s cancerous T cells.
They started with healthy T cells from a donor and set about modifying them.
The first base edit disabled the T-cell targeting mechanism so they wouldn’t attack Alyssa’s body
The second removed a chemical label, called CD7, which is found on all T cells
The third modification was an invisibility cloak that prevented cells from being killed by a chemotherapy drug
The last step of the genetic modification instructed the T-cells to go after anything with the CD7 mark so that it would destroy all the T-cells in his body, including the cancer cells. That is why this marking must be removed from the therapy – otherwise it will destroy itself.
If the therapy works, Alyssa’s immune system – including T cells – will be rebuilt with the second bone marrow transplant.
When the idea was explained to the family, mom Kiona thought, “Can you do that?” It was Alyssa’s decision to be the first to undergo the experimental therapy – which contained millions of modified cells – in May this year.
“She is the first patient to be treated with this technology,” said Professor Waseem Qasim, of UCL and Great Ormond Street.
He said this genetic manipulation was a “very rapidly evolving field of science” with “enormous potential” in a whole range of diseases.
Alyssa was left vulnerable to infection, as the synthetic cells attacked both the cancerous T cells in her body and those that protected her from disease.
After a month, Alyssa was in remission and received a second bone marrow transplant to boost her immune system.
Alyssa spent 16 weeks in hospital and couldn’t see her brother, who was still in school, in case he brought in any germs.
There were concerns after the three-month check-up again found signs of cancer. But his two most recent investigations have been clear.
“You just learn to appreciate every little thing. I’m so grateful to be here now,” Alyssa said.
“It’s crazy. It’s just amazing that I was able to have this opportunity, I’m very grateful for it and it will also help other children in the future.”
She watches Christmas, is a bridesmaid at her aunt’s wedding, gets back on her bike, goes back to school and “just does normal people stuff”.
The family hope the cancer never returns, but are already grateful for the time it has saved them.
“Having that extra year, those last three months when she’s been home, has been a gift in itself,” Kiona said.
Dad James said: “I find it quite difficult to say how proud we are. When you see what she has been through and her life vitality that she has brought to every situation, it is exceptional.”
Most children with leukemia respond to mainstream treatments, but it is thought that up to a dozen a year could benefit from this therapy.
Alyssa is just the first of 10 people to receive the drug in a clinical trial.
Dr Robert Chiesa, from the bone marrow transplant department at Great Ormond Street Hospital, said: “It is extremely exciting. Obviously, this is a new area of medicine and it is fascinating to be able to redirect the immune system to fight cancer.
The technology, however, only scratches the surface of what the base edition could achieve.
Dr David Liu, one of the inventors of Basic Editing at the Broad Institute, told me it was “a bit surreal” that people were being treated just six years after the technology was invented.
In Alyssa’s therapy, each of the basic modifications involved breaking a section of the genetic code so that it no longer worked. But there are more nuanced apps where, instead of disabling an instruction, you can fix a faulty one. Sickle cell disease, for example, is caused by a single base change that could be corrected.
So there are already basic editing trials underway in sickle cell disease, as well as in high cholesterol that runs in families and beta-thalassemia, a blood disorder.
Dr. Liu said that “therapeutic applications of base editing are just beginning” and that it was “humbling to be a part of this era of therapeutic human gene editing” because science was now taking ” key steps to take control of our genomes”.
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