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Tech & Science U.S. Trial Finds CRISPR-Edited Cells Are Safe In Cancer Patients

11:37  07 february  2020
11:37  07 february  2020 Source:   gizmodo.com.au

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For years, scientists have hoped to use the gene-editing technology CRISPR to help treat all sorts of diseases, including cancer . Now for the first time in the U . S ., researchers say they’ve shown that CRISPR - edited immune cells can be safely given to cancer patients and survive for up to nine

CRISPR gene- edited immune cells have been injected into three people with advanced cancer without any serious side effects, the first trial of its kind in the US . Many cancers involving blood cells are now treated by removing immune cells from individuals, adding a gene that makes them target

Above, a doctor prepares to modify the T cells of a cancer patient for CAR T-cell therapy. (Photo: Getty Images)© Photo: Getty Images Above, a doctor prepares to modify the T cells of a cancer patient for CAR T-cell therapy. (Photo: Getty Images)

For years, scientists have hoped to use the gene-editing technology CRISPR to help treat all sorts of diseases, including cancer. Now for the first time in the U.S., researchers say they’ve shown that CRISPR-edited immune cells can be safely given to cancer patients and survive for up to nine months—a finding that may signal CRISPR’s future as part of an emerging cancer treatment known as immunotherapy.

The idea that we can boost the human immune system to help it fight off cancer isn’t new. But it’s only recently that researchers have been able to make substantial advances in the field. There are different techniques, but one that’s received lots of attention involves reprogramming our immune system’s shock troops, known as T cells, to attack cancer. T cells are drawn out from a patient’s blood, grown and modified in the lab so that they target tumour cells, and then reintroduced back into the body.

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Preliminary data from an innovative clinical trial suggests CRISPR could be safe for use in cancer therapy. Researchers were able to safely remove, edit and return the cells to patients ' bodies. Safety was measured in terms of side effects, and the authors found that there were no serious side

Genetically editing a cancer patient ' s immune cells using CRISPR /Cas9 technology, then infusing those cells back into the patient appears safe and The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U . S

These engineered T-cell therapies are already extending the lives of patients living with cancers that would have been untreatable otherwise, but they have their drawbacks. Sometimes, the altered T cells can trigger a life-threatening overload of the immune system against the body. Other times, the T cells may not survive or be effective against cancer cells long enough for the therapy to work.

These negatives have led researchers to explore new ways we can modify T cells to boost their cancer-killing process as well as make them safer. And one leading candidate for such a booster has been CRISPR, according to study author Carl June, a cancer researcher at the University of Pennsylvania and one of the pioneers of T-cell therapy.

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While immune cells engineered to fight cancer , called CAR-T cells , have been used in patients for Similar tests of CRISPR - edited T cells are under way in China. And CRISPR Therapeutics, a In another trial , researchers are snipping a small piece of DNA out of cells in the eyes of people with an

The edited T cells are multiplied in the laboratory before being infused back into the patient . The ability to edit and remove these genes using CRISPR -Cas9 therefore provides a powerful tool to enhance the natural ability of human T cells to fight cancer .

“The promise of CRISPR has been in its flexibility to be able to target multiple needles in the haystack, if you will,” June told Gizmodo by phone.

One area of T-cell immunotherapy research, for instance, has involved genetically modifying the receptors found on the surface of T cells so that they can more easily recognise cancer-specific proteins made by tumour cells—a technique known as TCR therapy. A stumbling block for TCR therapy in experiments has been that the changes made to these T cells sometimes don’t stick or aren’t as potent or safe as they should be, in part because of interference from the T cells’ naturally expressed receptors.

Scientists like June have theorised that CRISPR, which uses enzymes to cut out and/or insert bits of DNA from a cell, can be safely used to knock down several of these natural hurdles at once, which would strengthen the TCR process. In a new paper published today in Science, June and his team detailed how they tested whether these edited cells can live in the human body without causing any unexpected problems.

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First Phase I clinical trial data with CRISPR -engineered T cells suggest the approach is feasible and safe , with the T cells persisting for months. The first U . S . Phase I clinical trial to evaluate CRISPR -Cas9- edited T cells in humans with advanced cancer has reported that the patients

2Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia You are going to email the following CRISPR -engineered T cells in patients with refractory cancer . Multiply gene- edited human immunological T cells demonstrate safety and prolonged persistence in

One significant concern was that since an important enzyme used by CRISPR is derived from bacteria, the introduction of CRISPR-edited T cells into the body could cause an immune response; this might then kill off the cells before they even got to work on a tumour. In the three patients they studied, all of whom had advanced cancer that hadn’t responded well to treatment, there was also the worry that their immune systems were so damaged by earlier therapies that the T cells wouldn’t survive for long.

“We found just to the contrary—that we have much longer survival of these cells. And at very high levels that have been really strong,” June said. “And we didn’t see any increase in immune response.”

The study is a Phase 1 clinical trial, meaning it was solely meant to test whether the approach is safe to use in people. So we can’t say yet whether CRISPR truly can boost the effectiveness and safety of TCR or other T-cell immunotherapies. (In China, CRISPR research in humans has progressed faster, though there have been concerns about the safety and ethics of these trials). But June and his team are hopeful that CRISPR is right on the cusp of not only improving cancer treatment but modern medicine in general. This trial also began in 2016, and in the years since, scientists have only gotten better at making CRISPR more effective and precise at editing DNA.

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Two other trials are CRISPR editing cells outside of the body to treat cancer or blood disorders. traffic_analyzer/getty images plus. There is a gene therapy, approved in 2017 by the U . S . Food and Drug Administration, for a type of Leber congenital amaurosis caused by a mutation in the RPE65 gene.

Editing cells ’ genomes with CRISPR -Cas9 might increase the risk that the altered cells , intended to But experts are taking the cancer -risk finding seriously. The CEO of CRISPR Therapeutics, Sam We need to do the work and make sure edited cells returned to patients don’t become cancerous .”

“I think now, CRISPR can extend to many different kinds of therapies, beyond cancer. And it won’t just be T cells,” June said, referencing the ongoing, promising human trials of CRISPR to repair the red blood cells of someone afflicted with the genetic disorder sickle cell disease. “It’s really going to be an amazing time in the next five years. Many diseases that were once lethal will now have a treatment.”

June and his team are already working on a larger human trial that will test CRISPR for CAR T-cell therapy, a treatment that’s already earned approval from the U.S. Food and Drug Administration for certain cancers but can cause serious side effects. As for the three patients in this study, one tragically died from their cancer last year, while the other two are still alive and on other forms of chemotherapy. According to June, they may be offered participation in the next trial, but it will depend on the criteria dictated by the FDA.

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