A revolutionary treatment has cured an incurable cancer in a teenage girl.
Alyssa, a 13-year-old from Leicester, became the first reported patient in the world to get a new type of CRISPR called base editing in May 2022.
Base-edited T cells at Great Ormand Street Hospital for Children (GOSH) in collaboration with UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) treated ‘incurable’ T cell leukemia. Alyssa, left her with zero detectable cancer cells, reported in a press release.
“Of course, I’m going to do it because after I do it, people will know what they need to do, one way or another,” Alyssa said in the press release.
Over the next few months, the outcome must be monitored and confirmed
Alyssa was diagnosed with T-cell acute lymphoblastic leukaemia (T-ALL) in 2021 and had previously had chemotherapy, a bone marrow transplant, and various cancer treatments. But it was all in vain, and her disease reappeared. There were no other treatment choices available at the time.
She enrolled in a clinical experiment to get genetically engineered CAR T-cells from a healthy donor. The cells were modified using modern base-editing techniques, allowing them to seek and kill malignant T-cells without attacking each other.
“This is pretty extraordinary,” said Dr. Robert Chiesa, Consultant in Bone Marrow Transplant and CAR T-cell Therapy at GOSH. “However, it is still a preliminary outcome that needs to be studied and validated over the following few months.”
“To be honest, we’re on a bizarre cloud nine – it’s fantastic to be home,” Alyssa’s mother, Kiona, said.
Researchers had to opt for an ‘unconventional’ CAR T-cell therapy
Leukemia is characterised by the rapid growth of abnormal blood cells in the bone marrow. Usually, bone marrow cells are all destroyed by chemotherapy before bone marrow being replaced by a transplant. The procedure is well-liked and generally effective, but if it doesn’t work, doctors may try a different strategy called CAR-T therapy.
However, it is difficult to treat T-cell leukemia with traditional CAR-T-cell therapy because T-cells, which are designed to recognize and attack cancer T-cells, also end killing each other during the manufacturing process before they can given as treatment, as per press release.
As a result, the researchers engaged in the procedure developed a new kind of CAR T-cell treatment to combat malignant T-cells via base-editing, a method that was only developed six years ago.
How does base editing work?
Single letters of the DNA code are chemically altered to alter T cells. The technique was used to multiple changes to healthy donor T-cells.
The donor T-cells are modified so that they are not attacked by the patient’s immune system. Eventually, the patients are given the modified CAR T-cells to detect and destroy T-cells in their bodies. Once the procedure is completed successfully, the patient will receive a bone marrow transplant to rebuild their immune system.
“This is a great demonstration of how, with expert teams & infrastructure, we can combine cutting-edge technologies in the laboratory with real outcomes in the hospital for patients. It is our most advanced cell technology to date and paves the way for other new treatments and ultimately a better future for sick children,” said Professor Waseem Qasim, Professor of Cell and Gene Therapy at UCL GOS ICH and Consulting Immunologist at GOSH.
Alyssa’s mother hopes her daughter’s treatment is proof the research is working. “Doctors have said the first 6 months are the most important and we don’t want to be too arrogant, but we still think, ‘If they can just get rid of him once, she’ll be fine.’ And maybe we’re right,” she said.