Researchers have infused cells edited using CRISPR-Cas9 into two patients in a trial conducted at the University of Pennsylvania, NPR reports today (April 16). A university spokesperson confirmed in an emailed statement to The Scientist that the trial is underway and that two patients, one with multiple myeloma and one with sarcoma, have been treated so far. The study is the first instance of patients in the US being treated with a CRISPR-based therapy.
In an interview with The Scientist in June 2018, the leader of the study, oncologist Edward Stadtmauer, explained that CRISPR would be used as a tool in a new type of immunotherapy. His team would filter T cells from the blood of eligible patients with cancer, then use the gene-editing technique to knock out three of the cells’ existing receptors and with a lentiviral vector insert the gene for a receptor called NY-ESO-1, a protein that appears on the surface of some cancer cells. The modified cells would then be expanded for a few weeks in the lab. Patients would receive a brief course of chemotherapy, after which the cells would be infused back into them.
In addition to cancer applications, researchers are exploring the use of so-called ex vivo CRISPR editing—in which cells are altered outside the body and then given to patients—to treat blood disorders such as β-thalassemia and sickle cell anemia. Other teams are working to develop therapies that would edit genes at fault in genetic diseases inside patients’ bodies.
Until now, only a relatively small number of studies have tried to use CRISPR to treat disease. And almost all of those studies have been in China, and have been aimed at treating various forms of cancer.
There’s now a clinical trial underway at the University of Pennsylvania using CRISPR for cancer treatment. It involves removing immune system cells from patients, genetically modifying them in the lab and infusing the modified cells back into the body.
The hope is the modified cells will target and destroy cancer cells. No other information has been released about how well it might be working. The study was approved to eventually treat 18 patients.
“Findings from this research study will be shared at an appropriate time via medical meeting presentation or peer-reviewed publication,” a university spokesperson wrote in an email to NPR.
But beyond the cancer study, researchers in Europe, the United States and Canada are launching at least half a dozen carefully designed studies aimed at using CRISPR to treat a variety of diseases.
What other diseases are they testing treatments for?
Two trials sponsored by CRISPR Therapeutics of Cambridge, Mass., and Vertex Pharmaceuticals of Boston are designed to treat genetic blood disorders. One is for sickle cell disease, and another is a similar genetic condition called beta thalassemia.
In fact, the first beta thalassemia patient was recently treated in Germany. More patients may soon get their blood cells edited using CRISPR at that hospital and a second clinic in Germany, followed by patients at medical centers in Toronto, London and possibly elsewhere.
The first sickle disease patients could soon start getting the DNA in their blood cells edited in this country in Nashville, Tenn., San Antonio and New York.
That study is noteworthy because it would be the first time scientists try using CRISPR to edit genes while they are inside the human body. The other studies involve removing cells from patients, editing the DNA in those cells in the lab and then infusing the modified cells back into patients’ bodies.
Finally, several more U.S. cancer studies may also start this year in Texas, New York and elsewhere to try to treat tumors by genetically modifying immune system cells.
What can go wrong with CRISPR? Are there any concerns?
Whenever scientists try something new and powerful, it always raises fears that something could go wrong. The early days of gene therapy were scarred by major setbacks, such as the case of Jesse Gelsinger, who died after an adverse reaction to a treatment.
The big concern about CRISPR is that the editing could go awry, causing unintended changes in DNA that could cause health problems.
There’s also some concern about this new wave of studies because they are the first to get approved without going through an extra layer of scrutiny by the National Institutes of Health. That occurred because the NIH and FDA changed their policy, saying only some studies would require that extra layer of review.
“Every human on the planet should hope that this technology works. But it might work. It might not. It’s unknown,” says Laurie Zoloth, a bioethicist at the University of Chicago. “This is an experiment. So you do need exquisite layers of care. And you need to really think in advance with a careful ethical review how you do this sort of work.”
The researchers conducting the studies say they have conducted careful preliminary research, and their studies have gone through extensive scientific and ethical review.
When might we know whether any of these experimental CRISPR treatments are working?
All of these studies are very preliminary and are primarily aimed at first testing whether this is safe. That said, they are also looking for clues to whether they might be helping patients. So there could be at least a hint about that later this year. But it will be many years before any CRISPR treatment could become widely available.