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Tested in Pediatric B-Cell Leukemia Experimental allogeneic gene-edited T cells may provide an “off-the-shelf” alternative to autologous chimeric antigen receptor (CAR) T-cell therapies for children with recurrent or refractory B–cell acute lymphoblastic leukemia, reducing treatment delays and costs, according to a study in Science Translational Medicine. In a phase 1 clinical trial, 4 of 6 children treated with the allogeneic CAR T cells achieved remission, paving the way for them to receive allogeneic hematopoietic stem cell transplants. T cells from healthy adult donors were edited at multiple gene sites using a nextgeneration CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9) lentiviral method. One edit enables the T cells to target CD19 receptors expressed by diseased lymphocytes. Another reduces rejection risk by disrupting a receptor chain that promotes graft-vs-host disease. A third edit enhances edited T-cell survival by eliminating a receptor targeted by alemtuzumab, a monoclonal antibody commonly used to kill lymphocytes before stem cell transplants. The edited cells were expanded and purified, producing enough to treat several dozen patients, and cryopreserved before infusion. The 6 children, aged 14 months to 11 years, were treated with chemotherapy and alemtuzumab to reduce lymphocytes before infusion with the edited T cells. Infused cell counts peaked at 7 to 14 days after infusion among 4 patients, but expansion was not detected among the other 2 children. After 28 days, the 4 patients now in remission were reconditioned for allogeneic stem cell transplant. This both depleted any remaining edited T cells and their potential toxicity, and provided a rapid hematologic recovery, the authors wrote. Of the 6 patients who were treated, 2 had refractory disease after the edited T-cell infusion. They did not receive stem cell transplants and eventually died. Two of the 4 who were in remission after infusion experienced relapse after stem cell transplant and eventually died. The remaining 2 children were still in remission at 12 and at 3 months after receiving stem cell transplants. Historically, the 3-year event-free survival in similar high-risk cohorts is about 15%. Overall toxicities were similar to previous CAR T-cell therapies targeting CD19 receptors, meeting the trial’s primary end point for safety. Although the study was not designed to evaluate efficacy, “salvage of 2 of 6 patients treated under this approach is encouraging, and further data from larger cohorts and their long-term outcomes will be required,” the authors wrote. The possibility of eliminating allogeneic stem cell transplant after the edited T-cell treatment may also be investigated, they added.