Following the first U.S. test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies - for months. The results from this Phase 1 clinical trial suggest the gene editing approach was safe and feasible, which until now has been uncertain, and the findings represent an important step toward the ultimate goal of using gene editing to help a patient's immune system attack cancer. CRISPR-Cas9 gene editing provides a powerful tool to improve the natural ability of human T cells to fight cancer. Though engineered T cell therapies are greatly advancing cancer treatment, whether CRISPR-Cas9 edited T cells would be tolerated and survive once reinfused into a human has been unknown. Here, focusing on three patients in their 60s with advanced cancers that didn't respond to standard treatments, Edward A. Stadtmauer and colleagues sought to test this. They removed T lymphocytes from these patients' blood and used CRISPR to delete genes from the cells that might interfere with the immune systems's ability to fight cancer. Next, the researchers used a virus to arm the T-cells to attack a protein typically found on cancer cells, NY-ESO-1. They infused the cells back into the patients and monitored cell engraftment and persistence. There were no toxicity-related side effects, the authors report, and the engineered T cells could be detected up to 9-months post-infusion. The work builds on earlier research developing adoptive T cell therapies led by Dr. Carl June, who was also part of this study. In a related Perspective, Jennifer Hamilton and Jennifer Doudna write, "these findings provide the cell engineering field with a guide for the safe production and non-immunogenic administration of gene edited somatic cells." They add: "The big question that remains unanswered by this study is whether gene-edited, engineered T cells are effective against advanced cancer," while also noting that the study by Stadtmauer and colleagues was restricted to editing protocols available in 2016, in which gene-edited T cells are likely less effective than they would be using newer technology available today.