Jiankui He, PhD
The development of cancer treatments and diagnostic tools using CRISPR/Cas9 and other gene-editing technology is a promising area of research in the United States, although the field is moving into human studies at a relatively slow pace. Outrage recently generated by reports that twin girls were born in China from genetically modified embryos has injected an additional note of caution into the research.
American regulatory officials called for better controls worldwide on human gene-editing experiments after Jiankui He, PhD, announced in November that he had successfully changed a gene in the twins’ embryos to confer resistance to HIV. He, who is an associate professor at Southern University of Science and Technology in Shenzhen, China, described the research in a YouTube video and later at the Second International Summit on Human Gene Editing.1,2
He’s statements about the research, which has not yet been presented in peer-reviewed form, sparked a debate about the ethics of the experiment.
The controversy comes at a time when ongoing efforts to move genetically modified cancer treatments from the lab to the clinic in the United States have been proceeding more slowly than some had hoped. Investigators at the University of Pennsylvania have started to enroll patients in a multicenter trial testing CRISPR-edited T cells, but other phase I trials that American investigators had hoped to launch in 2018 are not yet underway.
In China, the development of gene-edited anticancer therapies has progressed more rapidly. In June, Chinese investigators reported encouraging findings in a small phase I study of T cells engineered with CRISPR to knock out the PD-1 immune checkpoint in patients with metastatic PD-L1–positive non–small cell lung cancer.
Of 8 evaluable patients treated across 4 dosing cohorts, 2 reached stable disease and 6 progressed. The median progression-free survival was 7.7 weeks (range, 5.6-28.0). and the median overall survival was 42.6 weeks (range, 13.4-52.4).3
Additional CRISPR trials for potential anticancer therapies are ongoing in China, according to studies registered on ClinicalTrials.gov.
There are many other signs of progress in the field. The underlying technologies and techniques of gene modification continue to improve,4,5
and preclinical research continues to identify potential ways to apply tools such as CRISPR to cancer care. In addition, 2 groups are making plans for the first US human clinical trials of gene editing in sickle cell disease.6
“The preclinical results that different groups have achieved by using tools like CRISPR to modify immune cells have been, and continue to be, extremely promising. Many people, including me, are very eager to move to trials, but everyone understands the need for caution. That was true before the events in China, but when something like that happens, it’s natural for those with oversight responsibility to take a step back and make sure they have all the safeguards we need in place to prevent anything like that from happening again,” said Saad J. Kenderian, MB, ChB, a senior associate consultant in the Division of Hematology at Mayo Clinic in Rochester, Minnesota, who leads an immunotherapy engineering team.
“I don’t think the long-term picture has changed,” he said. “Promising treatments will move on to trials, and the process of getting trials designed and approved will speed up as we establish best practices. But we need to do it responsibly.”
The prospect of altering genes, even to cure illness, has long raised concerns about protecting human clinical study participants, but medical gene-editing efforts had gone 19 years without a major misstep.7
Then He announced that he had overseen the modification of the CCR5
gene in twin girls who had already been born and at least 1 other still-gestating fetus.
He said he recruited 8 couples who were undergoing in vitro fertilization (IVF) to avoid passing HIV from infected fathers to their children and proposed the genetic alteration as a means of greatly reducing the chance that any resulting children could contract HIV later in life.8
(Standard IVF techniques could have resulted in HIV-free children at birth, but people born without the CCR5
gene would be highly resistant to contracting HIV.)
According to He’s presentation, the modification successfully removed both copies of CCR5
in 1 girl but left 1 copy of the gene in the second child. He has not yet published an account of his work in any independent journal, and there are no reports of independent authorities examining the girls or their DNA.2