By Julie Steenhuysen

(Reuters Health) – The first test in the United States of the CRISPR gene-editing tool in cancer appears to be safe, but it’s too soon to know whether it’s effective, U.S. researchers reported on Thursday in the journal Science.

“The findings represent an important advance in the therapeutic application of gene editing and highlight the potential to accelerate development of cell-based therapies,” Jennifer Doudna of the University of California at Berkeley, who pioneered the gene editing technique, and her colleague Jennifer Hamilton write in an editorial.

The CRISPR approach has quickly become the preferred method of gene editing in research labs because of its ease of use compared with older techniques, and doctors have begun testing it to treat a number of diseases.

CRISPR-Cas9, used in this study, works like a pair of molecular scissors that can target and trim away parts of the genome and replace them with new stretches of DNA.

CRISPR has already shown promise at editing the genes of patients with beta thalassemia and sickle cell disease in clinical trials.

In the latest study, Dr. Edward Stadtmauer of the University of Pennsylvania in Philadelphia and colleagues tested it in three patients with advanced cancers. Two had the blood cancer multiple myeloma and one had sarcoma, a cancer that attacks connective tissues.

The researchers paired the use of CRISPR with a type of immunotherapy in which scientists harvest T-cells from a patient’s immune system, reprogram them to attack cancer cells and infuse them back into patients.

Engineered T cell therapies, such as CAR-T therapy (or chimeric antigen receptor T cell therapy), can produce long-lasting remission in patients with blood cancers. But the treatments don’t work for many other kinds of cancer, the immunity can wane and they can cause serious side effects.

Stadtmauer and colleagues sought to use CRISPR to address some of those issues. They took immune system cells from the patients’ blood and used the CRISPR-Cas9 system to delete genes from the cells that might hamper the immune system’s ability to fight cancer, and engineered the cells to recognize and attack cancer cells.

The team then infused these cells back into the patients and watched to see if they would multiply. So far, the researchers have not seen any toxic side effects. The engineered T-cells started growing in all of the patients and lasted for up to nine months after the infusion.

“Until now, it has been unknown whether CRISPR-Cas9 edited T cells would be tolerated and thrive once reinfused into a human,” Doudna writes. “The big question that remains unanswered by this study is whether CRISPR-edited, engineered T cells are effective against advanced cancer.”

The pilot study was designed to track safety. Larger trials will be needed to test for efficacy. At the end of the trial, one patient died from advanced cancer, and the other two were receiving other treatments.

A key concern with CRISPR-edited cells is that the technique has been shown to create some “off-target” or unintended edits in the genome.

Study co-author Dr. Carl June, an immunologist at the University of Pennsylvania who pioneered CAR-T cell therapy, said the team found two off-target effects.

One was a rare change in the DNA code that occurred in 1 in 1,000 of the edited cells. The other was a chromosome translocation, in which a chromosome reattached itself to the wrong chromosome. This occurred in fewer than 1.5 percent of the infused cells, June said in an email to Reuters Health.

The infused cells with these unintended edits did not survive as well as the correctly edited genes, he said.

Based on the promising safety profile, June said it’s likely that many academic centers and companies will try the technique in further clinical trials.

“We hope to work with companies to advance this but at this point, there are no firm plans,” he said.

SOURCE:, and Science, online February 6, 2020.