Severe acute leukemia, “modified” CAR-T cells used for the first time in the world

“If I can do it, others will know they can do it too. Yes, I will. And I will help others.” And Alyssa, a thirteen-year-old English girl originally from Leicester, may have really managed to defeat a very serious form of blood cancer that had struck her two years ago and which seemed to leave her no hope. And all thanks to an experimental therapy, never attempted before to treat that type of tumor, based on a “modified” version of CAR-T, immune system cells instructed to attack the diseased ones. The results of this trial, conducted by doctors from Great Ormond Street Hospital for Children (GOSH) and experts from University College of London, have just been presented at the annual meeting of the American Society of Hematology, currently underway in New Orleans: although it is too early to declare Alyssa definitively cured, say the clinicians, her story certainly represents an important stimulus to continue investigating the efficacy and safety of the treatment.

In fact, such a result was by no means a foregone conclusion. Alyssa had begun to feel sick in the first months of 2021, with seemingly unimportant symptoms: colds and other infections, a general sense of exhaustion, fevers. Symptoms that in reality, as the doctors discovered in May of the same year, depended on a serious form of blood cancer, T-type acute lymphoblastic leukemia. A disease characterized by an abnormal production of cells of the immune system (T lymphocytes , precisely) in the blood, marrow and other organs. An aggressive disease, which progresses very quickly, and against which, at the moment, two treatments are available, chemotherapy and bone marrow transplantation. Neither, unfortunately, had worked for Alyssa.

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There was still a small chance. The CAR-T, or, more precisely, a revised and corrected version of them. CAR-T is a cell therapy in which T lymphocytes taken from a patient are re-infused into his body after appropriate laboratory modifications that make them able to attack the tumour. A treatment that is giving interesting results for many blood cancers, but which in the case of T-type acute lymphoblastic leukemia is particularly complicated, precisely because it is the T lymphocytes themselves that are diseased, and you cannot take them and teach them to attack themselves themselves. The experts therefore had to work their wits and try another approach. They used T lymphocytes taken from a donor and genetically modified base by base, i.e. intervening with extreme precision on all the “letters” of the DNA, to make them universal (i.e. compatible with Alyssa), and above all to ensure that they recognized and attacked only the actually sick T lymphocytes: in short, they created and administered to the girl “CAR-T anti-T” intelligent enough not to risk killing each other under friendly fire.

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The whole thing, as it is easy to imagine, was extremely complex, but it was worth it: the CAR-T cells did their duty, destroying the diseased lymphocytes, and Alyssa subsequently underwent a second bone marrow transplant to rebuild from zero his immune system. Now, finally, she is back home and recovering her strength. And, most important of all, there is currently no trace of cancer in her body: “From when Alyssa was diagnosed with leukemia until the administration of modified CAR-T therapy – explained Robert Chiesa, transplant expert marrow and CAR-T therapy al Gosh – the girl had never gone into remission. Neither with chemotherapy nor after the first marrow transplant. Only after receiving this treatment and a second marrow transplant were we able to declare her leukemia free. It is a very important result, although it is still preliminary and Alyssa’s condition needs to be closely monitored over the coming months.”