Crispr'd Cells Show Promise in First US Human Safety Trial

It’s been over three years since US regulators greenlit the nation’s first in-human test of Crispr’s disease-fighting potential , more than three years of waiting to find out if the much-hyped gene-editing technique could be safely used to beat back tough-to-treat cancers. Today, researchers from the University of Pennsylvania and Stanford finally revealed the first published report describing the trial. The highly anticipated results showed that the procedure is both safe and feasible; the Crispr’d cells went where they were supposed to go and survived for longer than expected. They didn’t cure anyone’s cancer, but they didn’t kill anyone, either, which means the results hold significant promise for the future of Crispr-based medicines.
The trial was small—just three people—and designed only to assess the technique’s safety. Last year, each cancer patient received infusions of about 100 million of their own T cells, which had been genetically modified in a University of Pennsylvania lab. There, researchers equipped the cells with souped up cancer-recognizing receptors and used Crispr to make them more efficient killing machines. These cells successfully joined up with the rest of each person’s immune system and could still be found circulating in patients’ blood nine months later. The researchers presented some of that preliminary data at a conference in December, but didn’t include any information about how well the Crispr’d cells actually performed. That information is among the new details included in the peer-reviewed study published Thursday in Science.“Before we did this, no one had ever infused Crispr-edited cells into patients, and we’re encouraged by the fact that we could do it safely,” says Edward A. Stadtmauer, an oncologist at the University of Pennsylvania and the study’s principal investigator. “Now we can move on to a whole new frontier of further engineering these cells and expanding the number of patients treated.”
The study was overseen by Carl June, a pioneer of the emerging field of immunotherapy, which involves supercharging patients’ own immune systems to fight cancer through a series of genetic tweaks and pharmaceutical nudges . June’s biggest breakthrough came in 2012, when his UPenn lab inserted a new gene into the T cells of a terminally ill child named Emily Whitehead; imbued with new cancer-recognizing abilities, those cells wiped her leukemia off the map. In June, the now-14-year-old ran her first 5K to raise money for curing children’s cancer.Whitehead’s miraculous recovery wasn’t exactly a fluke. But she was lucky . The T cells she received triggered a “cytokine storm” that flooded her body with organ-damaging inflammation. June’s team saved her life by administering a newly-approved drug. But other patients haven’t been so fortunate. Reengineered T cells can also go wrong in other ways—natural receptors will sometimes interfere with the designer ones, making them less effective. The goal of the UPenn trial was to see if Crispr could solve some of those issues—without creating a dangerous immune system reaction. Previous research has shown humans to have existing immunity to the bacteria from which Crispr (the original version , which the UPenn team used) is derived.
Joseph Fraietta, who runs his own immunotherapy lab at UPenn’s Center for Advanced Cellular Therapeutics, designed the Crispr systems they used and supervised the editing. After harvesting T cells from three patients, his group made three edits to them. The first was to a gene called PDCD1. It makes a protein that acts like a brake on the immune system. Tumors have ways of turning up the expression of this protein in immune cells to dampen their response to the invading cancer. By using Crispr to turn off PDCD1, the scientists hoped to increase the likelihood that the patient’s new clone army of T cells would all show up to the fight.