Immune cells edited with CRISPR/Cas9 to
fight cancer seem
to be safe and long-lasting, a small safety test of the cells in three
cancer patients at the University of Pennsylvania shows.
All three had cancers that could not be
controlled by other therapies. While the gene-edited immune cells didn’t cure
their cancer, the cells stayed in the body up to nine months and didn’t cause any
serious side effects, researchers report February 6 in Science.
The result is an important milestone in the
gene editor’s journey toward being
used clinically (SN: 12/16/19).
But the Phase I clinical trial — which measures safety, not effectiveness — also
saw some errors
made during editing, one concern with the technology (SN: 3/5/19).
CRISPR/Cas9 is a two-part molecular tool
for cutting DNA. One part, a snippet of genetic material called a guide RNA,
leads the DNA-cutting enzyme Cas9 to specific spots in DNA where researchers
want to make a change. In this case, the team altered three genes in immune
cells called T cells. The edits were aimed toward making the T cells more
efficient than usual in killing cancer cells.
Most (93.5 percent to 100 percent) of the
cuts were right on target, but the gene editor made some cuts the researchers
didn’t intend. These “off-target” cuts plus deletions and rearrangements of
some DNA were found in a few edited cells. For instance, the sloppiest guide
RNA caused 7,778 on-target edits and only 38 off-target edits. In seven of
these off-target instances, the unwanted edits landed in the CLIC2 gene. Those edits are probably not
dangerous as that gene is not active in T cells anyway, the authors say.
Scientists worry that editing mistakes, deletions
and rearrangements may inactivate genes that restrict cell growth or create
cancer-promoting mutations. But edited T cells containing off-target edits in
the study didn’t appear to grow abnormally.
The researchers used versions of
CRISPR/Cas9 that were available in 2016, but the gene editor has since been improved
to increase efficiency and decrease off-target cutting. So future trials might
have more accurate editing, the researchers say.
