Gene-editing technology has been used to treat cancer for the first time, after doctors at London’s Great Ormond Street Children’s Hospital (GOSH) resorted to the previously untested method in a last-ditch attempt to save the life of a baby girl.
Special permission had to be sought before the technique could be used as it had not yet completed clinical trials, yet after all other treatments had failed to help one-year-old Layla, doctors felt it was worth a shot. The procedure involved injecting her with genetically modified white blood cells, called T-cells, which were engineered to seek out and destroy cancer cells, and produced positive results within a few weeks.
Layla had been diagnosed with acute lymphoblastic leukemia – a cancer of the white blood cells – at the age of just three months, with doctors describing her condition as “one of the most aggressive forms of the disease” they had ever seen. Because of this, chemotherapy was not strong enough to kill off the cancerous cells, leaving doctors with no alternative but to advise Layla’s relatives to start preparing for the worst.
However, her parents Ashleigh and Lisa urged them to try anything they could think of, even if it involved treatments that had never been tested before. The decision was then taken to supply her with the modified cells, despite the fact that doctors could not guarantee results.
These altered cells, called UCART19 cells, had been genetically altered using enzymes called TALENs which act like “molecular scissors,” capable of cutting specific DNA sequences in order to allow the insertion of new material. Derived from proteins produced by a type of pathogenic bacterium that affects a number of crop plants, TALENs have been found to work in pairs in order to cause a double-strand break in DNA sequences, meaning they slice across both strands of DNA rather than just one. They can be easily engineered to target any sequence, and offer a fast and efficient method of gene-editing that has the potential to revolutionize biological research, according to certain studies.
In this case, alongside tweaking the donor cells so that they would hunt and attack cancer cells, scientists also modified genes that ultimately granted the cells protection from the chemotherapy she was also given.
GOSH, in collaboration with University College London’s Institute of Child Health (UCL ICH) and biotechnology firm Cellectis, had been developing a bank of UCART19 cells created from donors, in preparation for the beginning of clinical trials. However, they decided instead to use their only vial of the cells on Layla. After several weeks, she developed a rash that indicated her immune system was responding, and one month later she was well enough to leave hospital.
Following the success of the procedure, full clinical trials on UCART19 cells are now scheduled to begin in early 2016, with Cellectis chairman and CEO Dr. André Choulika hoping that this could mark “the beginning of a revolution in cancer immunotherapy.” However, Professor Waseem Qasim of UCL ICH insists that “we have to be cautious about claiming that this will be a suitable treatment option for all children,” as it is yet to be tested on anyone other than Layla.
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