A teenager with an aggressive form of leukemia now has no detectable cancer cells in her body, thanks to an experimental therapy in which the 13-year-old received new, genetically-tweaked immune cells.
The patient, named Alyssa, seems to be in remission but will need to be closely monitored in the upcoming months to confirm that she's truly leukemia-free, according to Great Ormond Street Hospital for Children (opens in new tab) (GOSH) in the U.K., which provided the treatment. Previously, Alyssa had undergone chemotherapy and a bone marrow transplant, but her cancer kept coming back. Had she not entered a clinical trial (opens in new tab) for the experimental treatment, her only remaining option was palliative care to relieve her symptoms, rather than cure her cancer.
"I'm very honored, and it feels good to have helped other people as well," Alyssa said in a video released by GOSH (opens in new tab). She was the first patient to receive the new therapy. In all, her doctors aim to enroll a total of 10 patients between the ages of 6 months and 16 years old in their ongoing trial.
The team presented Alyssa's preliminary results on Saturday (Dec. 10) at the American Society of Haematology annual meeting (opens in new tab) in New Orleans, Louisiana.
Alyssa was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) in May 2021, according to GOSH. T-ALL affects stem cells in the bone marrow that would normally give rise to T-cells, white blood cells that guard the body against infection. In T-ALL, however, abnormal and immature T-cells build up in the body and crowd out the healthy T-cells, leaving patients prone to infections.
Treatments for T-ALL include chemotherapy, which kills the cancer cells, and bone marrow transplants, which replace patients' diseased stem cells with healthy ones from a donor. Unfortunately, as in Alyssa's case, these strategies don't always keep the disease under control.
"Approximately 20% of patients with T-ALL will relapse, and the prognosis for relapsed T-ALL is poor," according to a 2016 review in the journal Hematology ASH Education Program (opens in new tab).
A different treatment, called CAR-T cell therapy, has previously worked for other forms of ALL but not T-ALL. That therapy involves removing some of the patient's T-cells, tweaking their DNA in the lab and then reintroducing them into the body. The tweaked T-cells are meant to hunt down and kill cancer cells, but in T-ALL, the T-cells mistake each other for the enemy. Researchers at GOSH and the University College London (UCL) Great Ormond Street Institute of Child Health have been working on a way to prevent this friendly-fire.
For the new therapy, scientists stripped donated T-cells of certain receptors that would make them look foreign to the recipient's immune system. The cells also lost CD7, a protein found on all T-cells, and another protein called CD52, which is targeted by certain cancer treatments. Finally, the T-cells got a new receptor that let them target CD7-carrying T-cells, including cancerous ones, according to UCL (opens in new tab).
To apply all these genetic changes, the team used a modified form of the famous gene-editing tool CRISPR to swap out individual letters in the T-cells' DNA code. This technique is called "base editing." Alyssa is the first patient to receive a base-edited CAR-T cell therapy.
Within a month of treatment, Alyssa entered remission. She then received a second bone marrow transplant to restore her immune function, since the experimental therapy had wiped out her T-cells. Now, six months post-transplant, her cancer remains undetectable and she's recovering at home.
"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,'" Alyssa's mother, Kiona, told GOSH. "And maybe we’ll be right." Alyssa is hoping to return to school and "that could be a reality soon," her mom said.