Dana Farber Blog, Haining et al
A novel screening method using CRISPR-Cas9 genome editing technology has revealed new drug targets that could potentially enhance the effectiveness of PD-1 checkpoint inhibitors, a promising new class of cancer immunotherapy.
The method, developed by a team at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, uses CRISPR-Cas9 to systematically delete thousands of tumor genes to test their function in a mouse model. In findings published today by Nature, researchers led by pediatric oncologist W. Nick Haining, BM, BCh report that deletion of one gene, Ptpn2, made tumor cells more susceptible to PD-1 checkpoint inhibitors. Other novel drug targets are likely around the corner.
PD-1 inhibition “releases the brakes” on immune cells, enabling them to locate and destroy cancer cells. But for many patients, it’s not effective enough on its own.
“PD-1 checkpoint inhibitors have transformed the treatment of many cancers,” says Haining, senior author on the paper who is also affiliated with Harvard Medical School the Broad Institute of MIT and Harvard. “Yet despite the clinical success of this new class of cancer immunotherapy, the majority of patients don’t reap a clinical benefit from PD-1 blockade.”
That, Haining says, has triggered a rush of additional trials to investigate whether other drugs, when used in combination with PD-1 inhibitors, can boost response to the treatment.