iRC9-ΔCD19

iRC9-ΔCD19 is a research-stage genetic construct delivered via a gamma-retroviral vector, designed as a 'dual-switch' (DS) safety and selection platform for engineering CAR-T cell therapies. It is co-expressed in T cells alongside a chimeric antigen receptor (CAR) to provide controlled cell depletion and enrichment capabilities. The 'iRC9' component is a rapamycin-activated inducible caspase-9 suicide gene, which utilizes a heterodimeric switch where FKBP12-C9 is dimerized with FRB-C9 upon the administration of rapamycin. This mechanism triggers titratable apoptosis, allowing for the elimination of >80% of transduced T cells to manage potential off-tumor toxicities or cytokine release syndrome. The 'ΔCD19' component is a truncated, signaling-deficient version of the human CD19 surface antigen that serves as a selectable marker, enabling the enrichment of transduced T cells to high purity (>95%) using anti-CD19 microbeads. This platform has been investigated in preclinical models for treating CD123+ acute myeloid leukemia (AML) and HER2+ solid tumors.

Other names

inducible caspase-9-truncated CD19rapamycin-activated inducible caspase-9 and truncated CD19