Alyssa, a 13-year-old British girl, has been the first person in the world to have received a genetically modified CAR T cells (CART-T) (Chimeric Antigen Receptor T-Cell), a therapy that has revolutionized the treatment of blood cancers.
CART-T is not a medicine to use. It is a ‘living’ drug that is manufactured for each patient with a particular preparation: the cells of the patient’s immune system (T lymphocytes) are extracted, they are genetically modified to make them more potent and selective and they are reinfused into the patient,
In 2021, Alyssa was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and was treated with all current therapies, including chemotherapy and a bone marrow transplant. Unfortunately, her disease recurred and no further treatment options were available.
Alyssa was the first patient to enroll in a new clinical trial and in May she was admitted to the Bone Marrow Transplant Unit at Great Ormond Street Children’s Hospital, UK, to receive CART-T cells with genetically modified cells that originally came from a healthy donor. These cells had been edited using a new base editing technology to allow them to hunt down and kill cancer T cells without attacking each other.
Just 28 days later, Alyssa was in remission and received a second bone marrow transplant to restore her immune system. Now, six months later, she is home recovering with her family.
Addressing this type of T-cell leukemia with CAR-T has been complicated because T cells designed to recognize and attack cancer T cells also end up killing each other during the manufacturing process, before they can be delivered as a treatment. .
Therefore, researchers have employed a new genome editing technique called base editing to create a new type of CAR T cell therapy that can target cancer T cells. Base editing works by chemically converting individual letters of the DNA code (individual nucleotide bases) to change T cells.
The team used the technique to make multiple changes to T cells from healthy donors, meaning no cells need to be collected from the patient.
The researchers carried out the following steps: modifying the donor’s T cells so that they are not attacked by the patient’s own immune system; removing a ‘signal’ in the modified T cells so they won’t attack each other before they can be used as a treatment; deleting a second ‘signal’ that makes the cells invisible to other cancer treatments, and making the modified cells recognize and attack cancer T cells.
The result, he explains, are edited T cells that can be given to the patient so they quickly find and destroy T cells in the body, including leukemic T cells. If successful, the patient receives a bone marrow transplant to restore his depleted immune system.
The results, however, warns the immunologist Waseem Qasim, are preliminary, and must be monitored and confirmed in the coming months.
“Base editing is particularly promising, not only in this case, but also for genetic disorders,” says Robin Lovell-Badge of the Francis Crick Institute in London.
Alyssa is the first patient to receive this treatment during the trial, but the team aims to recruit up to ten T-cell leukemia patients who have exhausted all other treatment options. The researchers hope that if the trial is successful, the treatment can be offered to children earlier in their treatment process. They also hope that the technique could be an option for other types of leukemia.
The only other existing trial involving this base-editing technique began in New Zealand in July this year, reports “New Scientist.” A company called Verve Therapeutics hopes to show that this approach can treat an inherited genetic condition that causes dangerously high cholesterol levels.