A revolutionary therapy eliminates the girl’s incurable cancer

Alyssa

A teenage girl’s incurable cancer was eliminated from her body with the first use of a revolutionary new type of medicine.

All other treatments for Alyssa’s leukemia had failed.

So doctors at Great Ormond Street Hospital used ‘basic assembly’ to perform a feat of biological engineering to build her a new living drug.

Six months later the cancer is undetectable, but Alyssa is still being monitored in case it comes back.

Alyssa, 13, from Leicester, was diagnosed with T-cell acute lymphoblastic leukemia in May last year.

T cells are supposed to be the body’s guardians – seek out and destroy threats – but to Alyssa, they had become the danger and were growing out of control.

His cancer was aggressive. Chemotherapy, and then a bone marrow transplant, haven’t been able to rid it of his body.

Without the experimental medicine, the only option left would have been to simply make Alyssa as comfortable as possible.

“Eventually I was going to die,” Alyssa said. Her mother, Kiona, said she dreaded Christmas this time last year, “thinking this was our last one with her.” And then she “just cried” about her daughter’s 13th birthday in January.

What happened next would have been unthinkable just a few years ago and was made possible by the incredible advances in genetics.

The Great Ormond Street team used a technology called base editing, invented just six years ago.

The 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 make up words that carry meaning, the billions of strands in our DNA make up the instruction manual for our body.

Base editing allows scientists to zoom in on a precise part of the genetic code and then alter the molecular structure of just one base, converting it into another and changing the genetic instructions.

The large team of doctors and scientists used this tool to engineer a new type of T cell that could hunt down and kill Alyssa’s cancerous T cells.

They started with healthy T cells from a donor and started modifying them.

  • The first base change disabled the T-cell targeting mechanism so they wouldn’t assault Alyssa’s body

  • The second removed a chemical marker, 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 final stage of gene editing instructed the T cells to hunt down anything with the CD7 tag on it in order to destroy every T cell in its body, including cancerous ones. That is why this mark must be removed from the therapy, otherwise it will self-destruct.

If the therapy works, Alyssa’s immune system, including her T cells, will be rebuilt with the second bone marrow transplant.

BBC graphics

BBC graphics

When the idea was explained to the family, mom Kiona was left thinking, “Can you do this?” It was Alyssa’s decision to be the first to take the experimental therapy – which contained millions of modified cells – in May of this year.

Alyssa being treated

Jan Chu, senior research nurse at Great Ormond Street, gives Alyssa therapy in May 2022.

‘She is the first patient to be treated with this technology,’ said Prof Waseem Qasim, from UCL and Great Ormond Street.

He said this genetic manipulation was a “fast-moving area of ​​science” with “huge potential” in a range of diseases.

Alyssa remained vulnerable to infection, as the designer cells attacked both the cancerous T cells in her body and those that protect her from disease.

After a month, Alyssa was in remission and received a second bone marrow transplant to regrow her immune system.

Alyssa spent 16 weeks in hospital and was unable to see her brother, who was still in school, in case he carried germs.

There were concerns after the three-month checkup found signs of the cancer again. But his two most recent investigations have been clear.

“You just learn to appreciate every little thing. I’m so thankful to be here now,” said Alyssa.

“It’s crazy. It’s just amazing that I was able to have this opportunity, I’m very grateful for it and it will help other children too, in the future.”

Alyssa

Alyssa

She’s watching Christmas, being a bridesmaid at her aunt’s wedding, riding her bike back, going back to school, and “just doing normal stuff.”

The family hopes the cancer will never return, but are already grateful for the time it has bought them.

“Having this extra year, these last three months that she’s been home, has been a gift in itself,” Kiona said.

Dad James said: “I find it quite difficult to talk about how proud we are. When you see what he’s been through and his life vitality that he’s brought to every situation, it’s outstanding.”

Wasem Qasim

Prof Waseem Qasim was part of the team that developed core editing therapy

Most children with leukemia respond to mainstream treatments, but up to a dozen a year are thought to benefit from this therapy.

Alyssa is only the first of 10 people given the drug as part of a clinical trial.

Dr Robert Chiesa, from Great Ormond Street Hospital’s bone marrow transplant department, said: ‘It’s hugely exciting. Obviously, this is a new field of medicine and it’s fascinating that we can redirect the immune system to fight cancer.’

The technology, however, only scratches the surface of what basic editing 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 cured just six years after the technology was invented.

In Alyssa’s therapy, each of the basic changes involved breaking a section of the genetic code so that it no longer worked. But there are more nuanced applications where instead of disabling an instruction you can fix a faulty one. Sickle cell anemia, for example, is caused by just one base change that could be corrected.

So there’s already baseline editing evidence underway in sickle cell disease, as well as high cholesterol that runs in families and the blood disease beta-thalassemia.

Dr. Liu said that “therapeutic applications of basic editing are just beginning” and it was “humbling to be a part of this era of therapeutic human gene editing” as science was now taking “pivotal steps to take on the control of our genomes”.

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