Gene Therapy & Molecular Biology Volume 2 Issue A

A bone stromal cell line, D1, was stably transfected with both b-galactosidase and TK genes to allow for in vitro and in vivo localization and TK expression. The D1 cell line was selected because of its unique ability to localize to the bone upon intravenous injection. D1 cells expressed TK constitutively (D1-TK) and were able to exert strong bystander cell-kill upon the administration of ACV by inhibiting the growth of human prostate cancer cells when grown in vitro in tissue culture, in microgravity chambers, and in vivo as chimeric tumors. In vivo, the potent bystander effect exerted by D1-TK on C4-2 tumor growth was demonstrated radiographically, histologically, and was accompanied by a sharp decrease of serum PSA to a non-detectable level upon ACV administration.

We have demonstrated that stromal-epithelial interaction, which is vital to prostate cancer survival, can be interfered with by two novel gene therapy approaches in preclinical models of human prostate cancer.

Both adenoviral delivery of TK under transcriptional control by OC and a constitutive expression of TK by bone stromal cells elicit signiďƒžcant prostate cancer cell-kill, and warrant further development.

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