First Human Test of CRISPR Proposed

By Antonio Regalado

A federal safety board next week will consider the first human use of the gene-editing technology CRISPR, according to the National Institutes of Health.

The proposed treatment is an immune therapy in which a patient’s own blood cells will be removed and genetically altered using the technology, a type of molecular scissors able to precisely cut DNA.

The cancer treatment, in development by the University of Pennsylvania, is designed to target myeloma, melanoma, and sarcomas, according to the NIH.

CRISPR technology was invented less than four years ago but has rushed toward clinical application. A Cambridge company, Editas Medicine, previously said it intends to begin a trial in 2017 using CRISPR to treat a rare eye disease.

The new proposal to use CRISPR to edit human immune cells could happen sooner than that. The University of Pennsylvania didn’t immediately respond to a request for comment, and the timing of the study couldn’t be determined.

The same university helped pioneer a form of cancer therapy in which a person’s own blood cells are removed, genetically modified to attack cancer, and re-infused into the bloodstream. The type of cells being altered, called T cells, have the job of attacking and destroying bacteria as well as unhealthy cells.

The group reviewing the proposal, the Recombinant DNA Advisory Committee, was established to weigh the risks of studies involving gene therapy and also investigate reports of deaths and side effects. Modified T cells can be dangerous because they bypass the usual checks and balances that keep the immune system from attacking a person's own tissues. 

“While the application of new gene editing technologies in this field has great potential to improve human health, it is not without concerns,” Carrie Wolinetz, associate director of science policy at the NIH, said in a blog post.

Blood cells edited with other methods have previously been tried in humans to treat conditions including HIV and, in a previous instance, leukemia. But CRISPR technology is considered far easier to use. The Penn proposal offers an example of a new wave of designer cell therapies involving more extensive genetic engineering than was previously possible.

“Researchers in the field of gene transfer are excited by the potential of utilizing CRISPR/Cas9 to repair or delete mutations that are involved in numerous human diseases in less time and at a lower cost than earlier gene editing systems,” says Wolinetz. 

According to an abstract published by the NIH, Penn intends to undertake a small study in humans of T cells that are engineered to seek out myeloma and other cancers. What’s new is that the cells will also be edited to remove two genes.

One gene to be edited out, PD-1, is a key off switch of the body’s immune response. Without it, the T cells may overcome certain tumors’ ability to avoid detection. However, removing such controls could also present new risks to patients.  

 

Note from Team Cote: Due to the highly specialized nature of CRISPR technology, CRISPR is a prime candidate for developing new treatments for rare diseases. We are excited to see how the technology progresses in the coming years and hope to see more orphans treated by CRISPR in the future.