For patients with blood cancers like leukemia and lymphoma, the immunotherapy known as CAR-T cell therapy can be lifesaving. Doctors remove a patient’s immune cells, called T cells, engineer them in the lab to better recognize and attack cancer, and infuse them back into the bloodstream. But for solid tumors—which include lung, pancreatic, ovarian, colon, breast and other cancer types—these engineered immune cells still face too much resistance to effectively treat the disease.
Now, scientists at Gladstone Institutes and UC San Francisco (UCSF) have discovered a pair of genetic edits that make CAR-T cells more effective at infiltrating and fighting solid tumors. In mice, T cells with these edits dramatically outperformed standard CAR-T cells, clearing tumors in many cases where unedited CAR-T cells had little or no effect.
The discovery, published in Nature, was made using the world’s first in vivo genome-wide CRISPR screen in human T cells. Developed by the same team, this platform enabled researchers to study the effects of gene edits on CAR-T cells inside living mice across the entire genome, rather than only in isolated cell cultures in a dish.