Past June, Layla Richards, a one-year-old girl who had been diagnosed with an aggressive form leukaemia at 14 weeks old received a novel treatment at Great Ormond Street Hospital (GOSH) in London. The treatment, based on genome editing, had only hitherto been tested in the laboratory with mice.
Genome editing techniques have been gaining great importance in the current biomedical panorama in recent years. The technique involves modifying or removing specific sequences of cellular DNA to achieve a determined effect. The technique used in this case is known as TALENs (transcription activator-like effector nucleases), which consists of the binding of a DNA cleavage protein domain, i.e. a protein structure that cuts the DNA, to another DNA binding domain to target the desired sequence of the genome.
Given the severity of Layla’s leukaemia, the chemotherapy that she first underwent was ineffective. The novel possibility of genetically modifying the patient’s T-cells (immunological cells) so that they attack the cancer cells cannot be used either in cases as serious as Layla’s, as the patient does not have enough healthy T-cells. As a last resort, the doctors tried a bone marrow transplant to restore her damaged blood cells, but seven weeks after the transplant, the cancer reappeared. After this, the doctors informed the family that there were no more options and that only palliative care remained.
However, Layla’s parents did not want to accept palliative care, and asked that they try any treatment, even if it was experimental. The doctors at GOSH therefore contacted Waseem Qasim, an immunologist at University College London, who was working on an experimental treatment that could be applicable. The therapy was based on the use of TALENs to modify the T-cells of a healthy donor so that they can be effective in the patient’s body. The T-cells that present anti-leukaemia effects are known as CAR (chimericantigen receptor) 19-T cells. Using TALENs, the genome of these cells is modified in two ways: so that they are not attacked by the patient’s antibodies, and so that they do not attack the patient’s own cells. The result is so-called UCART19 cells.
The cancer cells disappeared.
Layla was given a single 1 ml dose of these cells and in two months the cancer cells had vanished. Following this, she underwent a further bone marrow transplant to replace her entire blood and immune systems; one month later, the little girl was able to go home with her family. Nevertheless, she has to return often to GOSH, where she is being monitored to check that she is recovering normally.
Although doctors remain cautious as regards drawing generalised conclusions, and it is too early to state categorically that Layla is cured, this experiment has nevertheless opened an avenue that could mean the establishment of a clinical treatment for leukaemia and other types of cancer. In 2016, the company that produces these cells, Cellectis, hopes to start a clinical trial with UCART19 cells in a larger group of patients. “[…] it could be the beginning of a revolution in cancer immunotherapy”, stated Dr. André Choulika, chairman and CEO of the company.
Although the therapeutic technique discussed here has particular medical interest, it also has an important bioethical aspect, as it paves the way for new treatments using procedures that in themselves do not have any ethical difficulty for implementation.