Scientists in China plan to use the genome-editing technology CRISPR-Cas9 in patients as early as next month, Nature reported on Thursday. If they go ahead, it would be the first time people would be injected with cells whose DNA has been altered by CRISPR.
A US proposal to run a similar study received approval by a federal ethics and safety panel last month, but it faces months of additional regulatory hurdles before it can go ahead by the end of 2016 at the earliest. The Chinese scientists, led by oncologist Lu You of Sichuan University’s West China Hospital in Chengdu, received approval from the hospital’s review board on July 6, Nature reported, and plan to treat their first patient in August.
Both the US and Chinese scientists would use CRISPR to edit immune-system T cells in patients with cancer in an effort to make those cells destroy malignant cells.
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Like the proposed US study, Lu’s would start by removing T cells from the blood of patients, in this case those with non-small cell lung cancer that has spread to distant sites in the body and no longer responds to treatment. Using CRISPR, his team would delete a gene for a molecule called PD-1. That molecule is a receptor on the surface of T cells, and is the Achilles’ heel of the immune system’s cancer-fighting efforts: Many tumors produce molecules that slip into PD-1 and turn off the T cell as effectively as a key turning off a car ignition.
Drugs that block this process, including Merck’s Keytruda (the drug that has successfully treated former President Jimmy Carter) and Bristol-Myers Squibb’s Opdivo, have recently raised hopes that the immune system can be unleashed on more cancers.
The CRISPR’d T cells would be coaxed to multiply in lab dishes, and then examined to make sure that only the PD-1 gene has been altered. (One concern about CRISPR is that it has “off-target effects,” deleting or changing genes it isn’t supposed to touch.)
If Lu’s team determines that the T cells are missing only their PD-1 gene, researchers would infuse the edited cells back into patients, where, if everything goes well, the T cells would attack the tumors. The trial will include 10 patients to start, with different doses of the cells to assess safety, according to Nature.
Last year, the Food and Drug Administration approved both Keytruda and Opdivo for non-small cell lung cancer, based on human studies showing that blocking PD-1 indeed frees T cells to attack those tumors. That suggests that a genome-editing approach to achieve the same molecular goal might also be successful.
CRISPR testing in China has previously leapfrogged that in other countries. Last year, for instance, scientists in China became the first to use CRISPR to edit the DNA of human embryos. (The embryos were nonviable.)
Genome-editing technology has raised the greatest concerns over its possible use in eggs, sperm, or early human embryos, called germline editing. Critics fear that could lead to “designer babies” with the altered DNA inherited by offspring. In April, Xiaomei Zhai of Peking Union Medical College told a US National Academy of Sciences panel on genome editing that “if the risk-benefit ratio is acceptable, a total ban on germline gene editing is not ethically justifiable.”