Gene Therapy of Prostate Cancer Using Radioactive Iodine

前列腺癌是美国男性癌症死亡的第二大原因。转移性前列腺 癌症被认为基本上是不治之症。与之形成鲜明对比的是，甲状腺癌可以被有效地治疗。 有时，即使出现广泛的转移，也能治愈，因为细胞有能力 浓缩碘，使放射性碘治疗成为可能和有效。中描述的研究 这项建议旨在转移甲状腺钠碘转运体(NIS)的基因，该结构 这是甲状腺细胞将碘捕获到前列腺癌细胞中的原因，这将允许使用 放射性碘。此外，这种转移作为转移的基因治疗手段的潜在作用。 前列腺癌被检查。这些研究涉及使用前列腺靶向表达NIS基因 为了实现前列腺特异性启动子的基因表达。我们完成的实验，在 之前的孢子资助期证明了NIS基因在体外和体内转移的可行性，以及 这种新型的基因靶向放射治疗将很快开始对患有局部癌症的男性进行I期临床试验。 复发性前列腺癌。续订建议书中概述的实验将1)完成第一阶段试验 并检查其结果；2)将第二代腺病毒投入临床试验，通过包含 前盆启动子驱动NIS表达是高度前列腺特异性的；以及3)发展复制型腺病毒 表达NIS的载体将对前列腺癌以及 全身给药后活性增加，从而针对转移性疾病。这些研究将 探讨NIS基因转移作为前列腺癌转移治疗方法的可能性 疾病，并是第一个这样描述的。此外，放射性碘效应在我们的 前列腺癌模型将有助于激发人们对NIS作为治疗其他癌症的基因的兴趣 类型。

Prostate cancer is the second leading cause of cancer death of American men. Metastatic prostate cancer is considered essentially incurable. In marked contrast, thyroid cancers can be effectively treated and, at times, cured even when widespread metastasis is present, because of the ability of the cells to concentrate iodine, making therapy with radioactive iodine possible and effective. The studies described in this proposal are aimed at transferring the gene for the thyroidal sodium-iodide symporter (NIS), the structure that is responsible for iodide trapping by thyroid cells, into prostate cancer cells, which will allow therapy with radioactive iodine. In addition, the potential role of this transfer as a means of gene therapy for metastatic prostate cancer is examined. The studies involve targeting expression of the NIS gene using prostate specific promoters in order to achieve prostate specific gene expression. The experiments we completed, in the previous SPORE funding period demonstrated the feasibility of NIS gene transfer in vitro and in vivo, and a phase I clinical trial will soon be opened of this novel genetically targeted radiotherapy for men with locally recurrent prostate cancer. The experiments outlined in renewal proposal will 1) complete the phase I trial and examine its results; 2) bring to clinical trial a second generation adenovirus that through inclusion of a probasin promoter driving NIS expression is highly prostate specific; and 3) develop replicating adenovirus vectors that express NIS that will offer higher efficacy and specificity towards prostate cancer as well as increased activity after systemic administration, thereby targeting metastatic disease. These studies will serve to examine the potential of NIS gene transfer to prostate cancer as a method of therapy of metastatic disease and are the first so described. In addition, successful demonstration of radioiodine effect in our prostate cancer model will serve to stimulate interest in NIS as a therapeutic gene for other cancer types.