Chinese scientists to begin first human CRISPR trial

Chinese scientists plan to start the first-ever clinical trial of CRISPR genome-editing technology in humans – on patients with lung cancer – this August.

The trial will primarily test the safety of the technique. It is similar to a planned US clinical trial using CRISPR to treat three types of cancer, which has received approval from the US Food and Drug Administration, but is still awaiting full approval to go ahead.

The planned treatment involves injected genetically edited immune T cells into patients with metastatic non-small-cell lung cancer who have failed to respond to conventional chemotherapy. 'Treatment options are very limited,' Dr Lu You, lead researcher and oncologist at Sichuan University West China Hospital, told Nature News. 'This technique is of great promise in bringing benefits to patients, especially the cancer patients whom we treat every day.'

The Chinese team will use CRISPR/Cas9 to delete a gene that encodes the PD-1 protein in T cells extracted from the patient's blood. The PD-1 protein normally keeps the immune system in check to prevent T cells from attacking healthy cells. These modified T cells will then be multiplied and injected back into the patient to activate an immune response against the cancer.

The trial will involve ten patients. For safety, the first three participants will be tested one at a time, and each one will be observed for two months before moving to the next patient.

The main safety concern is that, by deleting the PD-1 gene, the activated T-cells could attack healthy cells. However, trials involving PD-1 antibodies, which work in a similar way, have not shown these effects. Last November, a baby in London was also successfully treated for advanced leukaemia using T cells that had been modified using the genome-editing technique TALENs (see BioNews 827).

A second safety concern is that CRISPR could create 'off-target' effects – inadvertently deleting the wrong gene. But a biotechnology company collaborating on the trial, Chengdu MedGenCell, will examine all T cells to ensure the correct gene is deleted before the T cells are injected back into the patient.

Ethical approval for the trial took just six months, which is fast by western standards. There have been criticisms of China for not being cautious enough in this area. Chinese scientists were the first to genetically edit human embryos (see BioNews 799).  'When it comes to gene editing, China goes first,' Tetsuya Ishii, a bioethicist at Hokkaido University in Sapporo, Japan, told Nature News.