The world’s first clinical trial that will inject humans with genetically modified cells created with a ground-breaking DNA-editing technology is set to start in the month of August. The team, which received ethical approval on July 6 from the review board of the West China Hospital in Chengdu, will begin testing genetically altered cells on lung cancer patients in August. Chinese scientists will soon pioneer the use of a breakthrough gene-editing technique to inject modified cells on humans during clinical trials.
Led by oncologist Lu You from the Sichuan University, scientists will modify the cells using CRISPR-Cas9, a form of “genetic engineering scissors” that allows experts to edit DNA with precision.
“I hope we are the first,” Lu tells the scientific journal Nature. “And more importantly, I hope we can get positive data from the trial.” It is hoped it might provide a new treatment against cancer for patients who have not responded to chemotherapy or radiation therapy.
Lu and colleagues will enroll patients diagnosed with metastatic non-small lung cancer, as well as patients for whom radiation therapy, chemotherapy and other forms of treatment have failed. Accordin
g to Lu, current treatment options are very limited, but the CRISPR-Cas9 technique holds great promise in bringing benefits to patients, particularly to cancer patients.The researchers will extract T cells from the blood of patients taking part in the trail.
A gene coding for a protein called PD-9 will be knocked out in the cells using CRISPR-Cas9.
The technique uses tags and an enzyme to cut DNA in a precise place, allowing small portions of a gene to be removed.
This turns off the gene for PD-9, which will mean the T cells will loose some of the regulation that stops them from attacking cells belonging to the human body. These edited cells will be multiplied before being injected back into the patient. Researchers hope they will then home in on the cancer and destroy it. However, there are concerns the cells could become overactive and mount an immune response against healthy tissue too.
Previous research has shown that CRISPR can result in gene edits at the wrong place in the genome. Because of this, biotechnology company Chengdu MedGencell will validate the modified cells in the Chinese trial to make sure that the correct genes are removed.
Meanwhile, Timothy Chan from the Memorial Sloan Kettering Cancer Center is worried that the approach might trigger an excessive autoimmune response — the cells might start attacking the gut, the adrenaline glands or other healthy tissues. “All the T-cells – everything will be active,” says Chan. “That will be a concern.”
Chan suggests that the Chinese team take the T-cells from the site of the tumor, because they would already be specialized for targeting cancer. However, oncologist Lei Deng, who is one of the researchers in the Chinese study, says the lung cancer tumors targeted in the clinical trial cannot be accessed easily. Deng says the project is reassured by antibody therapies approved by the FDA. These therapies did not display a high level of autoimmune response.
Lu’s trial would be the first time CRISPR-Cas9 has been used in humans. The technique has previously been tested by Chinese scientists on human embryos and in monkeys and dogs. “I hope we are the first,” Lu told. “And more importantly, I hope we can get positive data from the trial.”
