Inducible caspase 9 safety switch (iCasp9, iC9)

The **inducible caspase 9 (iCasp9) safety switch** is a genetically engineered cell-suicide system used in the context of T-cell and other adoptive cell therapies to provide an emergency off-switch for the removal of potentially harmful cells. It consists of a modified human caspase 9 fused to an engineered drug-binding domain (usually a version of the human FK506-binding protein, FKBP). Upon administration of a specific small-molecule dimerizer drug (such as AP1903/rimiducid or AP20187), the fusion protein dimerizes and activates caspase 9's apoptotic function, triggering rapid apoptosis of the modified cell. This strategy enables precise, rapid, and efficient elimination—often more than 99%—of gene-modified, infused cells in vivo, such as CAR-T cells or virus-specific T cells, while sparing unmodified cells. The iCasp9 safety switch system is human-derived, minimizing immunogenicity, and does not affect cellular function until activated, providing a robust and widely adopted safety tool in experimental and clinical cell therapy protocols[1][4][5][7].

Other names

inducible caspase 9iCasp9iC9caspase 9 safety switchinducible human caspase 9suicide gene (when referring to cell therapies)iCasp9 safety switch

Small-molecule induced dimerization activates caspase 9, resulting in apoptotic cell death of transduced cells