World-first: Experimental CRISPR technology removes detectable cancer cells in 13-year-old

The result needs to be monitored and confirmed over the next few months

Alyssa was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) in 2021 and had already received chemotherapy, a bone marrow transplant, and other therapies for her cancer. However, it was all in vain, and her disease returned. At that point, there were no further treatment options available.

She became part of a trial to receive genetically modified CAR T-cells that originally came from a healthy donor. Using new base-editing technology, the cells were edited, thereby allowing them to chase and kill the cancerous T-cells without attacking each other.

"This is quite remarkable, although it is still a preliminary result, which needs to be monitored and confirmed over the next few months," said Dr. Robert Chiesa, Consultant in Bone Marrow Transplant and CAR T-cell therapy at GOSH.

"We're on a strange cloud nine, to be honest – it's amazing to be home," said Kiona, Alyssa's mum.

The researchers had to opt for an 'unconventional' CAR T-cell therapy

Leukemia is characterized by the sudden growth of abnormal blood cells that takes place in the bone marrow. Chemotherapy is usually administered to kill all bone marrow cells, and then, the bone marrow is replaced with a transplant. While the approach is popular and successful in most cases, doctors try another method called CAR-T therapy, if the above fails.

However, it is difficult to treat T-cell leukemia with traditional CAR T-cell therapy because T-cells designed to recognize and attack cancerous T-cells also end up killing each other during the manufacturing process before they can be given as a treatment, as per the release.

Therefore, the teams involved in the process used base-editing, a technique that was invented only six years ago, to create a new type of CAR T-cell therapy to attack cancerous T-cells.

How does base editing work?

Single letters of the DNA code are chemically converted to change the T-cells. The technique was used to make multiple changes to healthy donor T-cells.

The donor T-cells are edited and changed so that they aren't attacked by the patient's immune system. Eventually, the edited CAR T-cells are given to the patients to find and destroy T-cells in the body. Once successfully, the patient receives a bone marrow transplant to restore their depleted immune system.

"This is a great demonstration of how, with expert teams and infrastructure, we can link cutting-edge technologies in the lab with real results in the hospital for patients. It's our most sophisticated cell engineering so far and paves the way for other new treatments and ultimately better futures for sick children," said Professor Waseem Qasim, Professor of Cell and Gene Therapy at UCL GOS ICH and Consultant Immunologist at GOSH.

Alyssa's mother hopes her daughter's treatment is proof the research works. "The doctors have said the first six months are the most important, and we don't want to get too cavalier, but we kept thinking 'If they can just get rid of it, just once, she'll be ok.' And maybe we'll be right," she said.