Multiple genes simultaneously altered in immune cells
For the first time, researchers have used the gene scissors CRISPR/Cas9 (Crispr for short) to treat cancer patients. A group of researchers led by Carl June from the University of Pennsylvania in Philadelphia modified several genes in the genome of certain immune cells from three patients. The modified T cells were still able to kill cancer cells in the patients after up to nine months. There were no major side effects. The researchers speak of a “proof of concept” in the journal Science.
This is not the first time Crispr has been used in humans. At the end of November 2019, it was announced that two patients in Germany and the United States were probably successfully cured of their genetic blood diseases. However, that study is still ongoing, and the results have not been peer-reviewed or published in any journals. June’s study, on the other hand, has.
The research team first removed from the T cells’ genetic material genes for two receptors that the immune cells usually carry on their surface. They also cut from the T cells’ genome the gene for the receptor PD-1, which inhibits T cells under certain conditions.
Two patients had multiple myeloma, a form of blood cancer, and the third had a sarcoma that had already metastasized. First, blood was taken from them, from which the researchers isolated the T cells, whose genetic material they then modified. They multiplied the modified cells and injected them back into the patients’ blood.
It is true that the cancer was only slightly suppressed by the modified immune cells in one patient. Still, this is “the first confirmation of the ability of CRISPR/Cas9 technology to target multiple genes in humans simultaneously,” June said. Notably, this method avoids the sometimes life-threatening side effects of CAR T-cell therapy. There have been no serious side effects, he said.
“This study does not answer the big question of whether Crispr-edited T cells are effective against advanced cancer,” Jennifer Doudna, one of the developers of the CRISPR/Cas9 method, and Jennifer Hamilton, both of the University of California at Berkeley, commented on the work in Science. But they said the work is an “important advance” and illustrates “the potential to accelerate the development of cell-based therapies.” June shows that the method is applicable and safe, says Niels Halama of the German Cancer Research Center (DKFZ) in Heidelberg. However, the method is still “too costly and complex to be able to find its way into everyday clinical practice in the foreseeable future,” says Patrick Schmidt of the National Center for Tumor Diseases at the DKFZ. Gerald Willimsky, Head of Experimental and Translational Tumor Immunology at the Charité in Berlin, is confident: Since the start of the study in 2016, there have been many improvements in CRISPR/Cas9 technology.skb/dpa