Breakthrough Gene-Editing Therapy Reverses Incurable Blood Cancer in Patients

A treatment once considered the stuff of science fiction has succeeded in reversing aggressive, incurable blood cancers in some patients, doctors have revealed.

The therapy works by precisely rewriting the DNA of white blood cells, transforming them into a cancer-killing “living drug” that hunts down and destroys malignant cells.

The first child to receive the treatment whose case was first reported in 2022 remains cancer-free and now hopes to become a cancer researcher. Since then, eight more children and two adults with T-cell acute lymphoblastic leukaemia (T-ALL) have undergone the therapy, with almost two-thirds (64%) now in remission.

T-cells normally act as the body’s defenders, searching for and eliminating harmful threats. In T-ALL, however, these cells become cancerous and multiply uncontrollably.

For patients enrolled in the trial, standard treatments such as chemotherapy and bone-marrow transplants had already failed, leaving palliative care as the only remaining option.

“I genuinely believed I was going to die and would never grow up to do the things every child deserves,” said 16-year-old Alyssa Tapley from Leicester.

Alyssa became the first person in the world to receive the treatment at Great Ormond Street Hospital. Three years later, she is back to living a full life. The process involved destroying her existing immune system and rebuilding it from scratch. She spent four months in hospital and had to stay isolated from her brother to avoid infection.

Her cancer is now undetectable. She only needs annual check-ups and is currently completing her A-levels, working towards her Duke of Edinburgh Award, learning to drive, and planning a future in science.

“I’m looking at doing an apprenticeship in biomedical science and hopefully working in blood cancer research one day,” she said.

The team from University College London (UCL) and Great Ormond Street Hospital used an advanced technique known as base editing.

DNA is written in four chemical “letters”, or bases — adenine (A), cytosine (C), guanine (G) and thymine (T). The sequence of these bases forms the genetic instructions that control how the body develops and functions.

Base editing allows scientists to target a precise point in the genetic code and chemically convert one DNA letter into another, effectively rewriting faulty instructions.

Researchers aimed to harness the natural killing power of healthy T-cells and redirect it against the cancerous T-cells. This required a complex genetic redesign to prevent the therapeutic cells from destroying themselves or attacking the patient’s body.

They began with healthy donor T-cells and made four key genetic changes:

First, they switched off the cells’ normal targeting system so they would not attack healthy tissues.

Second, they removed a surface marker called CD7 found on all T-cells to stop the modified cells from killing each other.

Third, they made the cells resistant to a chemotherapy drug, allowing them to survive treatment.

Finally, they programmed the engineered cells to hunt and attack any cells displaying the CD7 marker.

As a result, the modified cells would destroy all other T-cells, whether healthy or cancerous, but not attack one another.

The engineered cells are infused into the patient, and if no cancer is detectable after four weeks, the patient proceeds to a bone-marrow transplant to rebuild the immune system.

“A few years ago, this would have sounded like science fiction,” said Prof Waseem Qasim of UCL and Great Ormond Street Hospital.

“We effectively have to dismantle the whole immune system. It’s an intense and demanding treatment, but when it works, it works remarkably well.”

The study, published in the New England Journal of Medicine, reports outcomes from the first 11 patients treated at Great Ormond Street and King’s College Hospital. Nine achieved deep remission and were able to proceed to bone-marrow transplantation.

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

One of the most serious risks is infection while the immune system is suppressed. In two cases, the cancer cells lost their CD7 marker, allowing them to evade the treatment and return.

“Given how aggressive this type of leukaemia is, these results are extremely striking,” said Dr Robert Chiesa from the bone-marrow transplant team at Great Ormond Street Hospital. “It’s very rewarding that we’ve been able to offer hope where there previously was none.”

Dr Deborah Yallop, a consultant haematologist at King’s College Hospital, added: “We’ve seen remarkable clearance of leukaemia that previously seemed untreatable this is an extremely powerful approach.”

Dr Tania Dexter, senior medical officer at the UK stem cell charity Anthony Nolan, said the results bring renewed hope: “For patients who previously had very low chances of survival, findings like these suggest that advanced treatments will continue to improve and reach more people.”