Breakthrough gene therapy offers hope for incurable cancers

Scientists in the UK have used a revolutionary new type of gene therapy to treat a young patient with relapsing T-cell leukaemia. Administering the technique – a world first – has raised hopes that it could soon help tackle other childhood cancers and serious illnesses.

Alyssa, from Leicester, had undergone chemotherapy and a bone marrow transplant in an unsuccessful attempt to relieve her leukemia. With no further treatments available, the outlook for the 13-year-old was bleak.

But after receiving an infusion of donated T cells, altered using a new technology known as base editing, Alyssa is recovering and has been in remission for six months.

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

Now the team at London’s Great Ormond Street Hospital (GOSH) who treated Alyssa are preparing to recruit 10 more T-cell leukemia patients, who have also exhausted all conventional treatments, for further trials. If these are successful, it is hoped that the modified cells can be given to patients with other types of leukemia and other diseases.

‘This is our most sophisticated cell engineering yet, and paves the way for other new treatments and ultimately a better future for sick children,’ said immunologist Professor Waseem Qasim, one of the project leaders. He will present the trial results at the American Society of Hematology meeting in New Orleans this weekend.

T-cell leukemia is cancer of a class of white blood cells known as T-cells. These fail to develop properly and grow too fast, 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 stop the progress of the disease and her only option seemed to be palliative care.

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

Other technologies can achieve such small changes, but are associated with more side effects. This is less of an issue with base modification and allowed Gosh’s team to make a separate set of 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 each other through ‘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 complete remission. After her modified cell therapy and a second bone marrow transplant to restore her immune system, she has been leukemia-free for more than six months.

“Doctors have said the first six months are the most important,” Kiona said. “We don’t want to get too dismissive, but we kept thinking, ‘If they can get rid of it, just once, he’ll be fine.’ And perhaps we will be right.

Crucially, Alyssa’s therapy relied on donated T cells that can be modified, so donor matching is not an issue. ‘This is an ‘off the shelf’ universal cell therapy and, if replicated, will mark a huge leap forward in these types of treatments,’ said Dr Louise Jones of the Medical Research Council, which funded the project.

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