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Made-to-measure vaccine overwhelms cancer cells

作者:宋徭    发布时间:2019-02-28 08:03:04    

By Abi Berger TWO cancer patients have been given vaccines that have been tailor-made to attack their particular cancers. These designer DNA vaccines are being pioneered by scientists at Southampton University Hospital and at the Centre for Protein Engineering in Cambridge, who believe that vaccines could one day replace conventional chemotherapy. The concept of cancer vaccines was born about three years ago, when scientists realised that it might be possible to persuade the body’s immune system to destroy cancer cells. For this to happen, the immune system must be able to pick out cancer cells and treat them as “foreign”. Cancer cells have unique proteins on their surface, and it is these that are being used to trigger the immune response. The teams in Southampton and Cambridge produce their vaccines by taking the DNA sequence that codes for a specific cancer protein and incorporating it into loops of DNA called plasmids. When they inject these engineered plasmids into the patient’s muscles, the muscle cells’ protein-making machinery starts to produce the cancer protein. The sudden appearance of millions of molecules of the cancer protein galvanises the immune system into producing billions of antibodies against it. The scientists hope that in the process of destroying these protein copies, the antibodies will also attack the proteins which are stuck to the surface of the cancer cells, and so destroy the cancer. The two patients to have cancer vaccines designed for them are suffering from lymphoma, a cancer of white blood cells. According to Freda Stevenson, an immunologist with the Southampton group, lymphomas are ideal cancers to work with because each lymphoma cell has a surface protein that is unique to that person. “We can take a biopsy from the patient’s lymphatic tissue, identify the DNA sequence which makes this unique protein on their cancer cells, and then splice this strand of DNA into plasmids to make the vaccine,” explains Stevenson. “The whole process takes just over a week for each patient,” she says. Earlier this year, Stevenson’s team showed that the technique works in mice. Not only did the mice produce antibodies to their own lymphomas, but the vaccine also stirred their “killer” white cells into action. These results spurred them to apply for approval to test the safety of the technique in humans. There are two potential problems with the technique, says Stevenson. The DNA carried by the plasmids might become incorporated into the patient’s own chromosomes, where it could switch on oncogenes. This would increase the chance of cancer developing. So far, there is “little evidence that this happens”, says Stevenson. The second concern is that introducing “naked” DNA into people could provoke a general anti-DNA response. In other words, the body might start to produce antibodies which could attack its own DNA, resulting in a type of autoimmune disease. Again, there has been no evidence that this happens. Scientists at Stanford University Medical School in California have been carrying out similar trials using vaccines made from the proteins themselves, rather than from the DNA which makes them. These vaccines take up to six months to prepare, but the results are encouraging. Two-thirds of Stanford’s 34 lymphoma patients have responded, and many have remained tumour free. “This demonstrates that we can manipulate the immune system to react against cancer cells,

 

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