John C. Morris, M.D.

NIS mediated gene therapy using radioiodine; a prostate cancer model. Our laboratory is studying the potential utility of the thyroidal iodide transporter (the sodium iodide symporter or NIS) as a therapeutic gene for gene therapy using prostate cancer as a model. We have induced prostate cancer cells to express NIS using an expression vector in which the NIS cDNA is coupled to the PSA promoter. This vector allows prostate specific and androgen sensitive NIS expression as measured by iodide trapping and western blotting. We have demonstrated this activity both in vitro and in vivo and have also shown that NIS expression can be induced by adenoviral mediated gene transfer into prostate cancer xenografts. This uptake is sufficiently high that the tumors can be effectively treated with radioactive iodine, achieving as high as 80% complete reponses. We are currently planning a phase I clinical trial of this therapy in men with recurrent prostate cancer confined to the prostate bed. In addition, we are also currently evaluating other tumor models for efficacy of radioiodine mediated gene therapy after NIS gene transfer, such as myleoma, hepatoma, and breast.