A revolutionary gene-editing method can create high-power immune cells that kill tumor cells for a longer time before they become “exhausted,” a study with a leukemia mouse model indicates.
Using the CRISPR/Cas9 editing method could lead to safer and more powerful immunotherapy for cancer patients, researchers say. The process, described in the article “Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumor rejection,” was published in the journal Nature.
Receptors are protein molecules on cell surfaces that recognize and respond to chemical signals. Chimeric antigen receptors (CARs) are synthetic receptors that scientists are investigating as a cancer therapy.
The technique involves removing a patient’s T-cells — which kill tumor cells — then implanting them with CARs that recognize a certain protein in the tumor cells, and re-introducing them into the patient. The modified T-cells can recognize the patient’s cancer and kill it.
At the moment, scientists use retroviral vectors – viruses safe for humans – to deliver the CAR gene to cells. But this method can have serious side effects because it delivers CARs to random locations.
That’s where CRISP/Cas9 comes in. The gene-editing tool allows scientists to cut and manipulate a cell’s DNA with precision.
Researchers from Memorial Sloan Kettering Cancer Center (MSK) have used the technique to deliver CARs to specific T-cell locations, an approach that could reduce harmful side effects.
The team also tested the method in a leukemia mouse model. They found that the reprogrammed T-cells were more powerful, killing cancer cells for a longer time before getting exhausted, compared with conventionally generated CAR T-cells.
“Cancer cells are relentless in their attempt to evade treatment, so we need CAR T-cells that can match and outlast them,” Michel Sadelain, PhD, senior author and director of the Center for Cell Engineering at MSK, said in a press release.
Sadelain and his team are planning the first clinical trials aimed at testing the effectiveness and safety of treatment with CRISPR-built T-cells.
“This new discovery shows that we may be able to harness the power of genome editing to give these ‘living therapies’ a built-in boost. We are eager to continue exploring how genome-editing technology could give us the next generation of CAR T-cell therapy,” Sadelain said.