Gene-Editing Tool May Better Deliver CAR T-Cell Immunotherapy
In mouse experiments, researchers have found that immune T cells that have been genetically engineered to express chimeric antigen receptors (CARs) using a new tool called CRISPR were more effective than CAR T cells that were engineered with conventional methods. The findings were reported in Nature (http://www.nature.com/nature/journal/v543/n7643/full/nature21405.html).
With CAR T-cell immunotherapy, patients’ T cells are collected, genetically modified to better attack cancer cells, expanded in a laboratory, and then administered back to the patients as treatment. With existing genetic engineering methods, scientists use a retrovirus to deliver CAR, but that can cause the gene to be inserted at random locations in the genome.
CRISPR allows scientists to precisely place the gene at the TRAC location in the T-cell genome, bypassing the chance with the conventional method that the CAR gene could disrupt the normal genome. The TRAC region includes the T-cell receptor, which helps the immune cells detect foreign molecules such as cancer cells.
In the mouse experiments, CAR T cells engineered with CRISPR were more effective at killing tumor cells and were much less likely to show signs of exhaustion (i.e., stop recognizing and attacking cancer cells after a certain time). Less than 2% of the CRISPR CAR T cells reached exhaustion, compared to almost half of the conventionally engineered CAR T cells.
Because the studies have only been conducted in mice, additional clinical trials are needed. However, the researchers noted that the technique may be less likely to result in random mutations in the genome and that it might have implications for treatments of other diseases as well.