inducible caspase 9

Inducible caspase 9 (iC9) is a pro-apoptotic "safety switch" or "suicide gene" technology designed to enhance the safety profile of cell and gene therapies, such as CAR-T cells and hematopoietic stem cell transplants. The system consists of a modified human caspase 9 protein fused to a chemical inducer of dimerization (CID) binding domain, typically a mutated FK506-binding protein (FKBP12). In its basal state, the iC9 protein remains monomeric and inactive within the engineered cells. Upon the administration of a specific small-molecule dimerizing agent, such as rimiducid (AP1903) or AP20187, the iC9 proteins undergo rapid dimerization. This dimerization mimics the natural activation process of caspase 9, triggering the intrinsic apoptotic pathway and leading to the rapid and selective elimination of the engineered cells. This mechanism allows clinicians to mitigate severe, life-threatening toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD) by effectively "turning off" the therapy.

Brand names

CaspaCIDe

Other names

inducible caspase 9 safety switchcaspase 9 suicide genecaspase9 suicide genecaspase-9 suicide geneiCasp9 safety switchiCasp-9 safety switchiCasp 9 safety switchCaspaCIDe