The study introduces an inducible caspase 9 (iCasp9) safety switch for adoptive cell therapy, designed to rapidly eliminate infused cells in case of adverse events. The iCasp9 system is based on the fusion of human caspase 9 to a modified human FK-binding protein, allowing conditional dimerization. When exposed to a synthetic dimerizing drug, AP1903, the iCasp9 becomes activated and leads to rapid cell death. The safety switch was tested in five patients who received haploidentical stem-cell transplants for relapsed acute leukemia. Patients with graft-versus-host disease (GVHD) were treated with AP1903, which eliminated more than 90% of the modified T cells within 30 minutes, effectively ending GVHD without recurrence. The iCasp9 system offers several advantages over existing suicide genes, including the use of a bioinert small molecule, reduced immunogenicity, and rapid efficacy. The study demonstrates the potential of the iCasp9 system to enhance the safety of cellular therapies and expand their clinical applications.The study introduces an inducible caspase 9 (iCasp9) safety switch for adoptive cell therapy, designed to rapidly eliminate infused cells in case of adverse events. The iCasp9 system is based on the fusion of human caspase 9 to a modified human FK-binding protein, allowing conditional dimerization. When exposed to a synthetic dimerizing drug, AP1903, the iCasp9 becomes activated and leads to rapid cell death. The safety switch was tested in five patients who received haploidentical stem-cell transplants for relapsed acute leukemia. Patients with graft-versus-host disease (GVHD) were treated with AP1903, which eliminated more than 90% of the modified T cells within 30 minutes, effectively ending GVHD without recurrence. The iCasp9 system offers several advantages over existing suicide genes, including the use of a bioinert small molecule, reduced immunogenicity, and rapid efficacy. The study demonstrates the potential of the iCasp9 system to enhance the safety of cellular therapies and expand their clinical applications.