Breakthrough gene therapy offers hope for incurable cancers | Research against cancer

British scientists have used a revolutionary new type of gene therapy to treat a young patient with relapsed T-cell leukaemia. Administration of the technique – a world first – has raised hopes that it may soon help address other childhood issues cancer and serious illnesses.

Alyssa, from Leicester, had undergone chemotherapy and a bone marrow transplant in an attempt to relieve her leukaemia, without success. With no other treatments available, the outlook for the 13-year-old was bleak.

But after receiving an infusion of donated T cells, modified using a new technology known as Core Editing, Alyssa recovers and has been in remission for six months.

“We are in a strange cloud nine to be honest. It’s amazing,” said her mother, Kiona.

Now the team at Great Ormond Street Hospital in London (Gosh) who treated Alyssa are preparing to enroll 10 more patients with T-cell leukemia, who have also exhausted all conventional treatments, for further trials. If these are successful, it is hoped that basic modified cells can be given to patients affected by other types of leukemia and other diseases.

“This is our most sophisticated cellular engineering to date, and it paves the way for other new treatments and ultimately a brighter future for sick children,” said immunologist Professor Waseem Qasim, one of the leaders of the project. He will present the results of the trial at the American Society of Hematology meeting in New Orleans this weekend.

T-cell leukemia is a cancer that affects a class of white blood cells called T cells. These do not grow properly and grow too quickly, interfering with the growth of blood cells in the body. Standard treatments include bone marrow transplants and chemotherapy. In Alyssa’s case, these failed to halt the progression of the disease and her only option seemed to be palliative care.

Head and shoulders shot of Waseem Qasim in hospital attire
Prof Waseem Qasim: “This paves the way for other new treatments.” Photograph: Great Ormond Street Hospital for Children

But recent advances in cell therapy have offered a new method to combat his condition. The T cells were taken from a healthy donor and modified so that they could kill other T cells, including his leukemic cells. This was done using Core Editing, which allows scientists to make a single change to the billions of letters of DNA that make up a person’s genetic code.

Other technologies can achieve such minute changes, but are associated with more side effects. This is less of an issue with the base edit and allowed the Gosh team to make a series of distinct modifications to the donated T cells. These complex alterations were necessary to ensure that the realigned T cells only attacked the leukemic T cells and did not destroy themselves with “friendly fire”. They also allowed cells to function after chemotherapy and also prevented them from affecting normal cells.

After her original treatments, Alyssa never achieved a full remission. After her modified cell therapy and a second bone marrow transplant to restore her immune system, she has been leukemia-free for over six months.

“The doctors said the first six months are the most important,” Kiona said. “We don’t want to be too cavalier, but we kept thinking, ‘If they can get rid of her, just once, she’ll be fine.’ And maybe we’ll be right.

The crux is that Alyssa’s therapy was based on T-cell donations that can be modified, so donor matching isn’t an issue. “This is a universal ‘standard’ cell therapy and – if replicated – will mark a huge step forward in these types of treatments,” said Dr Louise Jones of the Medical Research Council, which funded the project. .

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