A 13-year-old British girl with treatment-resistant leukemia is now in remission after receiving – in the world‘s first clinical trial of its kind – an infusion of immune cells modified with a more precise adaptation of the CRISPR technique, so as to target blood cancer. The young woman, who before the therapy had started palliative care, has been without traces of cancer for six months, even if it is too early to talk about definitive recovery.
THE CASE. The teenager, who is called Alyssa and lives in Leicester, was suffering from a form of leukemia that affects T cells, the white blood cells that recognize and neutralize cells infected by viruses or malignant tumor cells. She had undergone chemotherapy and a bone marrow transplant but the treatments had not been effective.
Leukemia is caused by an out-of-control growth of immune cells in the bone marrow and is treated by killing all these cells, diseased and healthy, with chemotherapy and then replacing them with a marrow transplant. This approach is usually effective, but if it fails, CAR-T therapy can be used.
The other options. CAR-T (Chimeric Antigens Receptor Cells-T) are engineered cells obtained in the laboratory starting from the patient’s T lymphocytes, which are taken, modified, multiplied and reintroduced into the body, only after having made them capable of recognizing in a targeted way certain types of cancer cells.
However, it is a very long, complex and expensive procedure, because it is personalized – that is, to be carried out on the cells of that single patient to avoid rejections. Sometimes then it is not possible to get enough T cells to engineer if the patient is already very ill.
Life saving engineering. Moreover, the girl’s leukemia was caused by T cells, and if CAR-T cells are modified so that they can attack other T cells, the risk is that they will kill each other canceling the procedure.
A team led by Waseem Qasim of University College London Great Ormond Street Institute of Child Health then took T cells from a healthy donor, made them able to eliminate diseased T cells (effectively producing CAR-T cells) but he then further altered the lymphocytes in order to disable the receptor that identified them as T cells and to make them act “undercover”.
Surgical modifications. To do this, it was decided to resort to editing of bases, a more precise form of the CRISPR molecular scissors which allows to carry out more precise and targeted interventions and to alter the single letters of the genetic code (the nucleotides) without cutting the double helix of DNA and thus reducing the risk of unwanted mutations.
How to correct a typo with a red pencil instead of tearing out the whole paper. Alyssa is the first person in the world to be treated with base-edited CAR-T cells. After 28 days from the infusion the patient was free from tumor cells.
Hope. The technique is particularly promising not only for the treatment of blood cancer but also for that of certain genetic diseases, also because it allows treating multiple patients with cells from a single donor, which does not necessarily have to be compatible because the cells can be altered . It will now be tested on 10 other patients with the same form of leukemia to further verify its effectiveness.