Breakthrough cell therapy leads to remission of 13-year-old girl’s incurable leukemia

A 13-year-old girl from the UK has achieved remission of an incurable blood cancer through an innovative cell therapy, still in experimental stages, which uses genetically modified immune cells from a healthy volunteer donor.

The announcement was made this Sunday (11) by British doctors during the annual meeting of the American Society of Hematology, in New Orleans (USA).

Alyssa had already been unsuccessfully treated with all available treatments for acute T-lymphoid leukemia. She had no choice but palliative care when she was enrolled in a clinical trial of a new treatment at Great Ormond Street Hospital for Children (Gosh ) from London.

This type of leukemia affects up to 20% of children and 40% of adults with blood cancer. The disease affects the cells of the immune system, the B and T lymphocytes, which protect against viruses.

“When there is a recurrence and the person has already been treated with chemotherapy and a bone marrow transplant, the prognosis is catastrophic”, explains hematologist Nelson Hamerschlak, from Hospital Albert Einstein (SP).

The new therapy, developed by researchers at the hospital and University College London, used cells from a voluntary donor, which were modified and applied to the patient to find and destroy cancer cells.

“Genetic manipulations were also used so that the cells were not rejected and to maintain their persistence [dentro do organismo]”, explains Hamerschlak.

The treatment is part of a technology known as CAR-T, which uses T cells, which act in the body’s defense. They are taken from the patient’s blood and genetically altered so that they fit on the surface of the cancerous particles and can attack them. The material is multiplied in the laboratory and reinserted into the patient.

The innovator of the new technique is having achieved a good result with cells modified from a donor. “The treatment cleans the person’s medulla so that he or she can receive a normal medulla transplant and regain immunity”, explains pediatric hematologist and oncologist Cláudio Galvão de Castro Júnior, who works at Hospital São Camilo and Instituto Hemomed.

About a month after receiving the modified cells, Alyssa experienced remission of the disease and received a second bone marrow transplant, with her own cells, to restore her immune system. Today, six months after the transplant, she is well at home, recovering from the transplant.

The therapy is still experimental, only tested in children and adolescents up to 16 years old, but the announcement was celebrated worldwide. “It’s revolutionary. First because it’s a donor CAR-T, second because it treats T-type acute lymphocytic leukemia [com recidiva]which was not treated before”, says Castro Júnior.

For him, the treatment will change the history of patients. “These T leukemias recur more and, when that happens, the treatment is very bad, there are many limiters. I manage to remember the little face of each patient that I lost in these situations. If I manage to change that with off-the-shelf CAR-T [tecnologia que já existe]it’s a revolution”, says the doctor.

CAR-T cell therapy considers the molecular characteristics of each type of cancer to design a specific response against the disease. They are already commercially available in Brazil for the treatment of type B acute lymphocytic leukemia and lymphomas, for example, but they still come up against the high cost.

A limitation of the current technique is the waiting time between the collection, handling and infusion of cells into the patient, explains Castro Júnior. Many patients do not survive to the end of this process. Another issue is that, due to the fact that the donor is the patient, the adequate amount of cells for the treatment is not always obtained.

The next step of the new technology will be to verify whether the transplanted cells will persist in the body. That is, even if Alyssa had remission of the disease, these transplanted cells could die and the cancer would return.

The girl was diagnosed with T acute lymphocytic leukemia in May 2021, after a long period of episodes that the family thought were colds, fatigue.

After the failure of conventional therapies, she was the first patient to be enrolled in the clinical trial of the new therapy and, in May 2022, she was hospitalized to receive modified cells from a voluntary donor.

According to the researchers, multiple additional DNA changes were needed to generate “universal” cell banks for the new study.

Previous treatments, for example, relied on techniques that altered the genes through cuts made by molecular “scissors”. The new approach works without causing breaks in the DNA, allowing more edits, with less risk of unwanted effects on the chromosomes.

The same researchers helped develop the use of modified T-cells (CAR-T) to treat B-cell leukemia in 2015. But these T cells, which were made to attack cancer cells, ended up killing themselves during the manufacturing process, which led to scientists to look for other solutions.

The technique is also being investigated to try to correct harmful changes in the DNA code for various inherited conditions.

“We’ve designed and developed the treatment from lab to clinic and are now testing it in children across the UK, in a unique bench-to-bedside approach. Cutting-edge technologies in the lab with real results in the hospital for patients. This opens up path to other new treatments and ultimately better futures for sick children,” said Waseem Qasim, professor of cell and gene therapy at University College London, in a statement.