Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

In order to gain tighter control on the expression of the very potent DT-A toxin, Peng et al [340] utilized a dual expression controlling system that relies both on transcriptional regulation and DNA recombination [376] [377] [378] . On the basis of their system, the chimeric modified enhancer/promoter sequence of the human prostate-specific antigen (PSA) gene, PSE-BC [371] , was used to regulate the expression of the Saccharomyces cerevisiae 2µ plasmid derived site-directed FLP recombinase. When prostate specific expression of FLP recombinase occurs, site directed DNA recombination that leads to DT-A gene expression takes place. The investigators showed eradication of PSA-expressing normal prostate cells and prostate cancer cells in culture, in xenografts and in a transgenic mouse model following adenoviral delivery of DNA encoding the prostate specific promoter-driven Flp recombinase and the Flp-responsive DT-A gene. Furthermore, Flp recombinase expression was shown to be regulated in a manner that correlates with the amount of PSA expression in these cells [340] .