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Gene-edited therapy transforms immune cells into cancer fighters
A groundbreaking treatment that rewrites the DNA of white blood cells has reversed aggressive, treatment-resistant leukaemia in nearly two-thirds of patients in a clinical trial, doctors report.
First patient remains cancer-free three years on
The first child treated with the therapy, whose case was documented in 2022, remains free of the disease and is now pursuing studies in biomedical science. Alyssa Tapley, 16, from Leicester, was the first patient worldwide to receive the treatment at Great Ormond Street Hospital. After four months of isolation to avoid infections while her immune system regenerated, she is now preparing for A-level exams, participating in the Duke of Edinburgh Award, and considering a career in blood cancer research.
"I really did think that I was going to die and wouldn't be able to grow up and do all the things that every child deserves to do," Tapley said. "Now I'm looking into an apprenticeship in biomedical science, and hopefully one day I'll go into blood cancer research."
How the therapy works
The treatment uses base editing, a precision gene-editing technique that alters individual letters of the genetic code. DNA is composed of four bases-adenine (A), cytosine (C), guanine (G), and thymine (T)-which act as instructions for the body. Base editing allows scientists to target a specific base, change its molecular structure, and effectively rewrite the genetic instructions.
In this trial, researchers modified healthy T-cells from donors to attack cancerous T-cells responsible for T-cell acute lymphoblastic leukaemia. Normally, T-cells defend the body against threats, but in this form of leukaemia, they multiply uncontrollably.
Four-step genetic modification
- First edit: Disabled the T-cells' targeting mechanism to prevent them from attacking the patient's own body.
- Second edit: Removed a chemical marker called CD7, present on all T-cells, to stop the therapy from self-destructing.
- Third edit: Added an "invisibility cloak" to shield the cells from chemotherapy drugs.
- Final edit: Programmed the T-cells to seek and destroy any cells bearing the CD7 marker, including cancerous ones.
After infusion, patients undergo a bone marrow transplant to rebuild their immune system if no cancer is detected within four weeks.
Trial results and risks
The study, published in the New England Journal of Medicine, involved 11 patients-eight children and three adults-across Great Ormond Street Hospital and King's College Hospital. All had exhausted conventional treatments, including chemotherapy and bone marrow transplants, leaving them with no options beyond palliative care.
Of the 11 patients, nine achieved deep remission, allowing them to proceed with bone marrow transplants. Seven remain cancer-free between three months and three years after treatment. However, two patients relapsed when their cancer cells lost the CD7 marker, enabling them to evade the therapy.
Prof Waseem Qasim, from UCL and Great Ormond Street, described the treatment as "deep, intensive" and "very demanding" for patients but noted that when successful, the results were "very well" achieved. "A few years ago, this would have been science fiction," he added.
Expert reactions
Dr Robert Chiesa, from the bone marrow transplant department at Great Ormond Street, called the results "striking" given the aggressiveness of the disease. "I'm very happy that we managed to offer hope to patients that otherwise have lost it," he said.
Dr Deborah Yallop, a consultant haematologist at King's College Hospital, described the therapy as "a very powerful approach," noting that it had cleared leukaemia in cases previously deemed incurable.
Dr Tania Dexter, senior medical officer at UK stem cell charity Anthony Nolan, said the results brought hope for advancing such treatments and making them accessible to more patients. "Considering these patients had a low chance of survival before the trial, these results are encouraging," she said.
Challenges and future outlook
The therapy carries significant risks, including infections while the immune system is suppressed. Patients must also contend with the physical and emotional toll of prolonged hospitalisation and isolation. Despite these challenges, experts believe the trial marks a major step forward in treating aggressive, treatment-resistant cancers.
Researchers are now exploring ways to refine the therapy, including addressing the risk of cancer cells evading detection by shedding the CD7 marker. The long-term goal is to expand access to such treatments and improve outcomes for patients with limited options.
