Science : Killer cells stalk cancerous protein

 作者:谈好奘     |      日期:2019-02-28 03:10:00
By Andy Coghlan CANCER cells that make a faulty version of a protein called p53 could in future be signing their own death warrants, if a treatment developed in the Netherlands fulfils its early promise. More than half of all human cancers make the defective protein. Healthy p53 helps prevent unwanted cell division, so when it becomes defective a tumour often forms. But Hans Nijman and his team at the Free University Hospital in Amsterdam have made immune system killer T cells that recognise and destroy cells making defective p53. The T cells have already been used to cure mice with tumours that make abnormal p53. T cells constantly “sniff” the cells they encounter to check whether they pose a danger to the body. Our cells display fragments of the proteins they contain. Those that are infected with a virus or bacterium display fragments of the invader’s proteins, and are destroyed. Nijman and his colleagues wanted to find T cells that would recognise cells displaying fragments of the defective p53. They injected mice with cancerous cells that make abnormally large amounts of the defective protein. The mice were specially bred to be unable to make p53 themselves, so their immune systems were more likely to treat p53 from the injected cells as a foreign and potentially dangerous protein. The mice produced millions of T cells targeted at different cell surface fragments, but the researchers exposed the cells to synthetic p53 fragments designed to mimic those from defective p53. This allowed them to isolate one type of T cell that latched tightly to one of the faulty p53 fragments. Nijman’s team has since grown large numbers of these T cells in laboratory cultures and shown that they are potent tumour killers. They injected the cells into 30 mice with p53-related tumours and all were cured within weeks. “We had 100 per cent success,” says Nijman. Healthy mice, however, were apparently unharmed. “It’s a dream, because we’ve proved that p53 is processed and presented on the surfaces of cells, and we’ve proved that you can target T cells against defective p53,” he says. “I’m very encouraged by this work,” agrees Hans Strauss, a tumour immunologist at the Royal Postgraduate Medical School in London. He adds that a team led by Robert Fenton of the US National Cancer Institute’s Frederick Cancer Research and Development Center in Frederick, Maryland, has recently achieved similar results with T cells programmed to destroy cells bearing ras, a protein that is overproduced in many types of cancer cell. Nijman says that additional experiments are under way in mice to confirm that the T cells do not trigger the immune system to attack the body’s own tissues. If these are successful, trials in people with colon and ovarian cancer could begin within 6 to 12 months. Initially, the researchers will inject patients with a fragment of defective p53 in the hope that this will trigger their immune systems to make T cells to fight their cancer. Subsequently, the Dutch team hopes to extract and grow T cells from individual patients,