Blood cancer therapy reverses incurable leukaemia in some patients

A therapy that would once have been considered a feat of science fiction has reversed aggressive, incurable blood cancers in some patients, doctors report.

The treatment involves precisely modifying the DNA of white blood cells to transform them into an anti-cancer “living drug”.

The first girl treated, whose story we reported in 2022, is still free of the disease and is now planning to become a cancer specialist.

Today, eight more children and two adults with T-cell acute lymphoblastic leukemia have been treated, with nearly two-thirds (64%) of patients in remission.

T cells are supposed to be the body’s guardians – seeking out and destroying threats – but in this form of leukemia, they spiral out of control.

For trial participants, chemotherapy and bone marrow transplants failed. Aside from experimental medicine, the only option left was to make their death more comfortable.

“I really thought I was going to die and I wouldn’t be able to grow up and do everything that every child deserves to be able to do,” said Alyssa Tapley, 16, from Leicester.

She was the first person in the world to receive treatment at Great Ormond Street Hospital and is now enjoying life.

The breakthrough treatment three years ago involved destroying his old immune system and developing a new one. She spent four months in the hospital and was unable to see her brother in case he brought her an infection.

But now her cancer is undetectable and she only needs annual check-ups. Alyssa is taking her A-levels, the Duke of Edinburgh Award, considering driving lessons and planning her future.

“I am considering doing an apprenticeship in biomedical sciences and hope that one day I will also go into blood cancer research,” she said.

The team from University College London (UCL) and Great Ormond Street Hospital used a technology called core editing.

The basics are the language of life. The four types of bases – 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 words that carry meaning, the billions of bases in our DNA spell out the instruction manual for our body.

Base editing allows scientists to zoom in on a specific part of the genetic code and then change the molecular structure of a single base, converting it from one type to another and rewriting the instruction manual.

The researchers wanted to harness the natural power of healthy T cells to seek out and destroy threats and turn them against T-cell acute lymphoblastic leukemia.

This is a tricky feat. They had to design the good T cells to chase out the bad ones without the treatment being wiped out.

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

The first basic modification disabled the targeting mechanism of T cells so that they could not attack the patient’s body.

The second removed a chemical label, called CD7, present on all T lymphocytes. Its removal is essential to prevent the therapy from self-destructing.

The third modification was an “invisibility cloak” that prevented cells from being killed by a chemotherapy drug.

The final step of genetic modification required the T cells to search for anything with CD7 markings.

Now the modified T cells would destroy any other T cells they found, whether cancerous or healthy, but they would not attack each other.

The treatment is infused into patients and if their cancer cannot be detected after four weeks, patients undergo a bone marrow transplant to regenerate their immune system.

“A few years ago this would have been science fiction,” says Professor Waseem Qasim of UCL and Great Ormond Street.

“We basically have to dismantle the entire immune system.

“It’s a deep, intensive treatment, very demanding for patients, but when it works, it works very well.”

The study, published in the New England Journal of Medicine, reports results from the first 11 patients treated at Great Ormond Street and King’s College Hospital. It shows that nine of them achieved a deep remission which allowed them to benefit from a bone marrow transplant.

Seven remain disease-free between three months and three years after treatment.

One of the biggest risks of treatment is infections when the immune system is suppressed.

In two cases, the cancer lost its CD7 markings, allowing it to hide from treatment and rebound in the body.

“Given the aggressiveness of this particular form of leukemia, these are quite striking clinical findings and, obviously, I am very pleased that we have managed to offer hope to patients who would otherwise have lost it,” said Dr Robert Chiesa of the Bone Marrow Transplant Unit at Great Ormond Street Hospital.

Dr Deborah Yallop, consultant haematologist at King’s, said: “We have seen impressive responses in eliminating leukemia that seemed incurable – it’s a very powerful approach.”

Commenting on the research, Dr Tania Dexter, Chief Medical Officer of the British Stem Cell Association Anthony Nolan, said: “Given these patients had little chance of survival before the trial, these results provide hope that treatments like this will continue to progress and become available to more patients. »