A teenage girl’s incurable cancer was eradicated in the first application of a revolutionary new type of medicine.
All other treatments for Alyssa’s leukemia had been ineffective.
Doctors at Great Ormond Street Hospital used “base editing” to perform a feat of biological engineering and create a new living drug for her.
Six months later, the cancer is no longer detectable, but Alyssa is still being closely monitored in case it recurs.
Alyssa, 13, of Leicester, was diagnosed with T-cell acute lymphoblastic leukemia last May.
T-cells are supposed to be the body’s guardians, searching for and eliminating threats, but for Alyssa, they had become the threat and were out of control.
Her cancer was particularly aggressive. Chemotherapy and a bone marrow transplant were ineffective in removing it from her body.
The only option without the experimental medicine would have been to make Alyssa as comfortable as possible.
“I would have died eventually,” Alyssa explained. Kiona, her mother, said she was dreading Christmas last year, “thinking this is our last with her.” Then, in January, she “just cried” through her daughter’s 13th birthday.
What happened next would have been unthinkable just a few years ago, but incredible advances in genetics have made it possible.
The Great Ormond Street team used a technology known as base editing, which was developed only six years ago.
Bases are life’s language. Our genetic code is made up of four types of bases: adenine (A), cytosine (C), guanine (G), and thymine (T). Just as letters in the alphabet spell out words with meaning, the billions of bases in our DNA spell out our body’s instruction manual.
Base editing enables scientists to zoom in on a specific section of the genetic code and then change the molecular structure of just one base, converting it to another and changing the genetic instructions.
This tool was used by a large team of doctors and scientists to create a new type of T-cell capable of hunting down and killing Alyssa’s cancerous T-cells.
They began with healthy T-cells from a donor and worked their way up.
The first base edit disabled the T-cell targeting mechanism, preventing them from attacking Alyssa’s body.
The second procedure removed a chemical marker known as CD7, which is found on all T-cells.
The third change was an invisibility cloak that prevented chemotherapy drugs from killing the cells.
The final stage of genetic modification instructed the T-cells to look for anything with the CD7 marking on it and destroy all T-cells in her body, including cancerous ones. That is why this marking must be removed from the therapy; otherwise, it will self-destruct.
If the treatment is successful, Alyssa’s immune system, including T-cells, will be rebuilt with a second bone marrow transplant.
When the plan was explained to the family, Kiona’s reaction was, “You can do that?” In May of this year, Alyssa made the decision to be the first to receive the experimental therapy, which contained millions of the modified cells.
Prof Waseem Qasim of UCL and Great Ormond Street Hospital said, “She’s the first patient to be treated with this technology.”
He called genetic manipulation a “very fast-moving area of science” with “enormous potential” for treating a variety of diseases.
Alyssa was left vulnerable to infection because the designer cells attacked both cancerous and protective T-cells in her body.
Alyssa was in remission after a month and was given a second bone marrow transplant to rebuild her immune system.
Alyssa was in the hospital for 16 weeks and couldn’t see her brother, who was still in school, for fear of bringing germs in.
There were concerns after the three-month check-up revealed new signs of cancer. Her two most recent investigations, however, have been unequivocal.
“You simply learn to appreciate everything. I’m just thankful that I’m here now “Alyssa stated.
“It’s insane. It’s incredible that I’ve been given this opportunity; I’m grateful for it, and it will benefit other children in the future.”
She’s looking forward to Christmas, being a bridesmaid at her auntie’s wedding, riding her bike again, going back to school, and “just doing normal people stuff.”
The family is hoping that the cancer will not return, but they are grateful for the time it has given them.
“Having this extra year, these last three months when she’s been home, has been a gift in and of itself,” Kiona said.
James, the father, stated: “It’s difficult for me to express how proud we are. It’s incredible to see what she’s been through and the zest for life she’s brought to every situation.”
Most children with leukemia respond to standard treatments, but this therapy may benefit up to a dozen children per year.
Alyssa is the first of ten people who will receive the drug as part of a clinical trial.
Dr. Robert Chiesa of Great Ormond Street Hospital’s bone marrow transplant department stated: “It’s incredibly exciting. This is obviously a new field in medicine, and it’s fascinating that we can redirect the immune system to fight cancer.”
However, the technology only scratches the surface of what base editing is capable of.
Dr. David Liu, one of the Broad Institute’s base editing inventors, told me it was “a little surreal” that people were being treated only six years after the technology was invented.
Each of Alyssa’s base edits involved breaking a section of genetic code so that it no longer worked. However, there are more nuanced applications in which, instead of turning off an instruction, you can repair a faulty one. For example, sickle-cell anaemia is caused by a single base change that can be corrected.
As a result, there are already trials of base editing in sickle cell disease, high cholesterol that runs in families, and the blood disorder beta-thalassemia.
Dr. Liu stated that the “therapeutic applications of base editing are just getting started,” and that it was “humbling to be a part of this era of therapeutic human gene editing,” as science was now taking “key steps toward taking control of our genomes.”