CRISPR cancer therapy trial gets go-ahead in US

The first in-human use of the genome-editing technology CRISPR has been approved by a US federal safety board.

The National Institute of Health's (NIH) recombinant DNA research advisory committee (RAC) last week approved a proposal for an early-stage trial that will test the safety of CRISPR to treat patients with three types of cancer: myeloma, melanoma and sarcoma.

The trial, proposed by scientists at the University of Pennsylvania (see BioNews 856), involves editing genes in T cells – a type of white blood cell. It will involve around 15 cancer patients and will be carried out at three centres: the University of Pennsylvania, MD Anderson Cancer Center in Houston, and the University of California at San Francisco.

The researchers will remove T cells from the patients and edit them in three ways – using CRISPR – before injecting the cells back into the patient. The first CRISPR edit will insert a protein engineered to detect cancer cells and instruct the T cells to target them, and the second will remove a protein that could interfere with this process. The final edit will prevent the cancer cells from disabling the T cells, by removing the gene that identifies the T cells as immune cells.

During the committee meeting, one of the concerns raised was a potential conflict of interest as one of the researchers holds patents on T-cell technologies and could stand to benefit if the trial is successful. Another concern was the history of gene technologies at the University of Pennsylvania – in 1999, an early gene-therapy trial by researchers at the university resulted in the death of 18-year-old Jesse Gelsinger, and a subsequent investigation found serious problems with the study, including unreported data on the therapy's adverse effects in animals.

'Any first use in humans we have to be extraordinarily careful,' Professor Laurie Zoloth, a bioethicist at Northwestern University in Evanston, Illinois, told Nature News. However, the decision by the committee was unanimous, with only one member abstaining.

Following the approval from the NIH, the research team will now have to seek approval from the US Food and Drug Administration – which regulates clinical trials in the US – as well as review boards at their own institutions, in order to carry out the trial. However, Professor Carl June, an immunologist at the University of Pennsylvania who is a science adviser on the project, told Nature News that the trial could begin by the end of the year.

The research is being funded through a charitable foundation set up in April by tech billionaire Sean Parker to give $250 million in funding to six cancer centres.

The NIH approval could see more trials involving CRISPR being proposed, including one from Editas Medicine in Massachusetts, which is planning a clinical trial using the technology to treat a rare form of blindness (see BioNews 828).