Immunology is evolving rapidly in the medical field. A recent article of mention is the NEJM Nov 2011 issue that talks about the inducible apoptosis as a safety switch for adoptive cell therapy.
This article is more of a cancer paper that discusses an inducible T cell safety switch that was based on the fusion of human caspase 9 to a modified human FK-binding protein - allowing for dimerization. Eventually, when exposed to a synthetic dimerizing drug, caspase 9 was induced and activated leading to cell death. So, they tested this hypothesis using the stem cell transplant model and GVHD treatment. Five patients who had undergone stem-cell transplantation were treated with the genetically modified T cells. A single dose of dimerizing drug, given to four patients in whom GVHD developed, eliminated more than 90% of the modified T cells within 30 minutes after administration and ended the GVHD without recurrence.
Interesting, look back at the literature on icasp9, this was tested apparently in erythropoietin transgene expression in animals. The effectiveness of the caspase-9-based artificial "death switch" as a safety measure for gene therapy based on the erythropoietin (Epo) hormone was tested in vitro and in vivo using the chemical inducer of dimerization. They concluded that inducible caspase 9 did not interfere with gene transfer, gene expression or tetracycline control and may be used as a safety mechanism for gene therapy.
This iCasp9 cell suicide system is interesting and perhaps might have role in Renal transplantation. It seems that prior hematology literature have Unclear how successful it would be in a solid organ transplant model. Any thoughts?