SHARON LEES/GOSH
THIS WEEK leukaemia – the disease that Layla had – for whom conventional therapies had not worked, 29 are still in remission months or years after treatment. There are now 77 trials of CAR T-cells around the world, for treating several different cancers of the blood. It is not a miracle cure, of course. CAR T-cells can cause adverse reactions by overstimulating the immune system, particularly in adults. Cancer cells can evolve to dodge the T-cells, by no longer expressing the target protein. Another issue is that a patient’s T-cells have to be removed, genetically modified and replaced. If T-cells from a donor are used, the donor cells will view all of the patients’ cells as foreign and attack them. This makes the treatment expensive – and in some cases, like Layla’s, doctors can’t get enough T-cells to modify. She was too small and sick. –Layla is recovering from leukaemia– This is where gene editing comes in. With conventional gene therapy, it is only possible to add genes. With gene editing, though, genes can also be disabled – opening up new, vital role in suppressing cancers. drugs – called PD1 inhibitors – that cheaper, possibilities. There are immune cells called stop cancers turning off T-cells are The Great Ormond Street team T-cells, for instance, that travel producing good results when was able to use donor T-cells to around the body seeking and combined with other therapies. treat Layla because in addition destroying abnormal-looking Another encouraging approach to the CAR gene, they used gene cells that may be infected or is to genetically engineer T-cells editing to disable the gene for turning cancerous. They detect to target cancers. Cancer cells the protein that recognises these cells with the help of protein often have proteins on their other cells as foreign, thereby receptors on their surface. surface seldom found on healthy preventing the donor cells from It is usually only when cancers cells. T-cells can be programmed attacking Layla’s healthy cells. manage to evade these hunters The result, at least in this one “There are lots of genetic that they become dangerous. case, was spectacular. “It’s tricks we can exploit to And cancers have some clever incredibly encouraging,” says make immune cells more tricks to do this. For example, Waseem Qasim of University specific and potent” T-cells have a receptor on their College London, who helped to surface called PD-1, which acts as develop the treatment. “There are an off switch. It is used to stop to recognise these by giving them a whole bunch of other disorders cells becoming overactive and genes for tailor-made receptors we can now create fixes for.” running amok. Many cancers called chimeric antigen receptors The aim of this work is to evolve ways of flicking the PD-1 (CARs). Biologists first began develop “off the shelf” CAR T-cell therapies, so that hundreds of switch and deactivating any work on CARs in the 1980s, but it people can be treated with the T-cells that try to attack them. is only in the past few years that same batch of cells. Many of the most promising human trials have begun – and Even so, in many cases there is new cancer treatments involve some results have been dramatic. yet another hurdle to overcome, boosting the immune response. In one trial involving 53 For instance, a new generation of children with acute lymphoblastic because the patient’s own
Layla’s gene-editing legacy Michael Le Page
WHAT comes next? Last week, it was announced that a 1-year-old girl called Layla has been saved from leukaemia by an experimental gene therapy. It was used as a last resort after all other treatments had failed. It’s too early to know whether Layla is free of cancer, or if the technique that saved her will work for others. But it is clear that gene editing is set to make an existing method of tackling cancer – genetically engineering immune cells to kill cancer cells – even more powerful and widely available. “There are lots of genetic tricks we can exploit to make the cells more specific and more potent,” says Adrian Thrasher, who heads the gene therapy programme at Great Ormond Street Hospital in London, where Layla was treated. Our immune systems play a 10 | NewScientist | 14 November 2015