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<\/p>\nFirst CRISPR clinical trial gets green light from US pane<\/b><\/a>l<\/p>\n<\/div>\n<\/div>\n There have been a number of human clinical trials using an alternative gene-editing technique, including one led by June, that have helped patients combat HIV<\/a>. June is also a scientific adviser on a planned US trial that would also use CRISPR\u2013Cas9-modified cells <\/a>for the treatment of cancer.<\/p>\n Last month, an advisory panel of the US National Institutes of Health (NIH) approved that project. But the trial also requires a green light from the US Food and Drug Administration (FDA) and a university review board. The US researchers have said they could start their clinical trial by the end of this year.<\/p>\n The Chinese trial will enrol patients who have metastatic non-small cell lung cancer and for whom chemotherapy, radiation therapy and other treatments have failed<\/a>. \u201cTreatment options are very limited,\u201d says Lu. \u201cThis technique is of great promise in bringing benefits to patients, especially the cancer patients whom we treat every day.\u201d<\/p>\n Leukaemia success heralds wave of gene-editing therapies<\/b><\/a><\/p>\n<\/div>\n<\/div>\n Lu\u2019s team will extract immune cells called T cells from the blood of the enrolled patients, and then use CRISPR\u2013Cas9 technology<\/a> \u2014 which pairs a molecular guide able to identify specific genetic sequences on a chromosome with an enzyme that can snip the chromosome at that spot \u2014 to knock out a gene in the cells. The gene encodes a protein called PD-1 that normally acts as a check on the cell\u2019s capacity to launch an immune response, to prevent it from attacking healthy cells.<\/p>\n The gene-edited cells will then be multiplied in the lab and re-introduced into the patient\u2019s bloodstream. The engineered cells will circulate and, the team hopes, home in on the cancer, says Lu. The planned US trial similarly intends to knock out the gene for PD-1, and it will also knock out a second gene and insert a third before the cells are re-introduced into the patient.<\/p>\n Last year, the FDA approved <\/a>for use against lung cancer <\/a>two antibody-based therapies that block PD-1<\/a>. But it is difficult to predict for any given patient to what extent these antibodies will block PD-1 and activate the immune response.<\/p>\n Gene-editing research in human embryos gains momentum<\/b><\/a><\/p>\n<\/div>\n<\/div>\n By contrast, knocking out the gene blocks PD-1 with greater certainty, while multiplying the cells increases the chance of a response. \u201cIt will be much more powerful than the antibodies,” says Timothy Chan, who does clinical research in immunotherapy at Memorial Sloan Kettering Cancer Center in New York City.<\/p>\n It is well known that CRISPR can result in gene edits at the wrong place<\/a> in the genome, with potentially harmful effects. Chengdu MedGenCell, a biotechnology company and a collaborator on the trial, will validate the cells to ensure that the correct genes are knocked out before the cells are re-introduced into the patients, says oncologist Lei Deng of West China Hospital, who is a member of Lu\u2019s team.<\/p>\n Because the technique targets T cells, which are involved in various kinds of immune responses, in a non-specific way, Chan worries that the approach might induce an excessive autoimmune response in which the cells would start attacking the gut, or adrenaline glands or other normal tissue. \u201cAll the T cells \u2014 everything will be active. That will be a concern,\u201d says Chan.<\/p>\n The unsung heroes of CRISPR<\/b><\/a><\/p>\n<\/div>\n<\/div>\n He suggests, instead, that the team take T cells from the site of the tumour, because they would already be specialized for attacking cancer. But Deng says that the lung-cancer tumours targeted by their trial are not easily accessible. He also says that the team is reassured by the FDA-approved antibody therapies, which did not show a high rate of autoimmune response.<\/p>\n The phase I trial is designed foremost to test whether the approach is safe. It will examine the effects of three different dosage regimens on ten people, and, Deng says, the team plans to proceed slowly, increasing the dosage gradually and starting with just one patient, who will be monitored closely for side effects. But the researchers will also closely watch markers in the blood that would indicate that the treatment is working.<\/p>\n Lu says that the review process, which took half a year, required that the team invest a lot of time and human resources, including close communication with the hospital\u2019s internal review board (IRB). \u201cThere was a lot of back and forth,\u201d he says. The NIH\u2019s approval of the other CRISPR trial \u201cstrengthened ours and our IRB\u2019s confidence in this study\u201d, he adds.<\/p>\n China has had a reputation for moving fast \u2014 sometimes too fast \u2014 with CRISPR, says Tetsuya Ishii, a bioethicist at Hokkaido University in Sapporo, Japan.<\/p>\n Bioethics in China: No wild east<\/b><\/a><\/p>\n<\/div>\n<\/div>\n According to Lu, his team was able to move fast because they are experienced with clinical trials of cancer treatments.<\/p>\n June is not surprised that a Chinese group would jump out in front on a trial such as this: \u201cChina places a high priority on biomedical research,\u201d he says.<\/p>\n Ishii notes that if the clinical trial begins as planned, it would be the latest in a series of firsts for China in the field of CRISPR gene editing, including the first CRISPR-edited human embryos<\/a>, and the first CRISPR-edited monkeys<\/a>. \u201cWhen it comes to gene editing, China goes first,\u201d says Ishii.<\/p>\n \u201cI hope we are the first,” says Lu. “And more importantly, I hope we can get positive data from the trial.\u201d<\/p>\nIneffective chemo<\/h2>\n
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<\/p>\nValidated cells<\/h2>\n
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<\/p>\nFast reputation<\/h2>\n
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