Live and Let Die: A New Suicide Gene Therapy Moves to the Clinic

Abstract

The concept of suicide gene therapy dates from the beginning of the field of gene therapy and was one of the first clinical applications. Initially described as an anticancer therapy, it quickly found a specific application in the practice of hematopoietic stem cell transplantation. A recent publication by Di Stasi et al. presents the first clinical data on a relatively new suicide gene system that targets caspase 9–mediated apoptosis in an inducible fashion.1 Specifically, five children undergoing haplo-identical stem cell transplantation for leukemia received donor T lymphocytes that had been genetically engineered with the inducible caspase 9 (iCasp9) gene. Four of the five patients developed graft-vs.-host disease (GVHD) caused by the donor lymphocytes that was quickly reversed by induction of the iCasp9 suicide gene. These results further validate the findings of others that suicide gene therapy for the control of GVHD is a valuable clinical procedure and, in the broader context, may have implications for a variety of other gene therapy applications in which a suicide safety switch may be useful.