CRISPR gene-edited immune cells have been injected into three people with advanced cancer without any serious side effects, the first trial of its kind in the US. It is also the first CRISPR cancer trial in the world to publish its findings, and the encouraging results will pave the way for many more trials.
“It’s an important milestone,” says Waseem Qasim at the UCL Great Ormond Street Institute of Child Health in the UK, who is carrying out a similar trial there.
The US trial was intended only to assess safety. The three participants had tumours that hadn’t responded to other treatments, and were given only one dose of gene-edited cells.
“Is it safe and feasible?” says team member Edward Stadtmauer at the University of Pennsylvania. “I think that’s what we demonstrated.”
Many cancers involving blood cells are now treated by removing immune cells from individuals, adding a gene that makes them target cancer cells and putting them back in the body.
But this treatment doesn’t work for everyone, says Stadtmauer. And in some, it works at first but they later relapse.
The hope is that using gene editing to delete genes in addition to adding the targeting gene will make this approach even more effective. For instance, immune cells have a safety switch, called PD-1, that other cells can flip to say “don’t hurt me”. Many cancers exploit this to avoid immune attacks.
In this trial, the team removed immune cells from three people who had tumours with the same protein on their surface. A virus was used to add a gene to make the immune cells target this protein.
Did You See This CB Softwares?
37 SOFTWARE TOOLS... FOR $27!?Join Affiliate Bots Right Away
Next, three genes, including PD-1, were deleted using CRISPR. After six weeks, the cells were put back in the individuals, where they survived for at least 9 months.
There were two big safety concerns. Firstly, CRISPR can cause unintended changes to genomes that could turn cells cancerous. Deleting three genes means cutting around each one in three spots in the genome, for instance, and the wrong ends can be joined up. This did happen in some cells, but there was no sign of any turning cancerous.
The other worry was that lingering traces of the CRISPR protein used for gene editing might trigger an immune reaction, since it is a bacterial protein. There was no sign of this.
The trial won’t continue because its 2016 gene-editing technology is already outdated, says Carl June, also at the University of Pennsylvania. In particular, a new form of CRISPR called base editing can be used to inactivate genes without cutting DNA, which should reduce the cancer risk even further. “We are very attracted to that,” says June.
There are also many other ways to edit immune cells to make them more effective, says Stadtmauer. “The possibilities are limitless based on our imagination and scientific focus.”
In particular, Stadtmauer wants to create “off-the-shelf” cells that could be given to any patient, rather than modifying each patient’s own cells. This would speed up treatments and greatly reduce costs.
Qasim’s team has already saved lives in an ongoing trial at Great Ormond Street using off-the-shelf cells created by an older form of gene editing called TALEN. But these cells have to be given as part of a drastic treatment, which is followed by a bone marrow transplant that kills off the edited cells. Stadtmauer wants to create cells that can survive indefinitely in people’s bodies.
The risk of edited cells turning cancerous or starting to attack healthy cells would be higher if they survive longer. But it is also possible to add a self-destruct mechanism triggered by a specific drug to kill them off if necessary.
There have been a number of trials of CRISPR-edited immune cells for treating cancer in China, but no results have yet been published.
Journal reference: Science, DOI: 10.1126/science.aba7365
More on these topics: