Gene Therapy of Prostate Cancer Using Radioactive Iodine

使用放射性碘治疗前列腺癌

• 批准号: 7729543
• 负责人: JOHN C. MORRIS
• 金额: $ 17.76万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-11 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7729543
• 关键词: Adenovirus Vector; Adenoviruses; American; Automobile Driving; Cancer Etiology; Cancer Model; Cells; Cessation of life; Clinical; Clinical Trials; Data; Disease; Dose; Failure; Funding; Gene Expression; Gene Transfer; Generations; In Vitro; Iodides; Iodine; Malignant neoplasm of prostate; Malignant neoplasm of thyroid; Maximum Tolerated Dose; Metastatic Prostate Cancer; Methods; Neoplasm Metastasis; Outcome; Patients; Phase I Clinical Trials; Phase II Clinical Trials; Prostate; Radiation therapy; Radioactive Iodine; Recurrence; Reproduction spores; Role; SLC5A5 gene; Safety; Specificity; Structure; Targeted Radiotherapy; Thyroid Gland; Thyroid carcinoma; Time; Tissues; Treatment Protocols; cancer cell; cancer type; gene therapy; human SLC5A5 protein; in vivo; interest; men; novel; probasin; promoter; research study; sodium-iodide symporter; therapeutic gene

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.

前列腺癌是美国男性癌症死亡的第二大原因。转移性前列 癌症被认为基本上是不可治愈的。与此形成鲜明对比的是， 有时，即使存在广泛的转移，由于细胞的能力， 浓缩碘，使放射性碘治疗成为可能和有效。中描述的研究 该建议旨在转移甲状腺钠碘同向转运体（NIS）的基因，其结构 它负责甲状腺细胞捕获碘，进入前列腺癌细胞，这将允许用 放射性碘此外，这种转移作为转移性肿瘤基因治疗手段的潜在作用也是一个挑战。 检查前列腺癌。这些研究涉及使用前列腺素靶向NIS基因的表达， 前列腺特异性启动子，以实现前列腺特异性基因表达。我们完成的实验， 上一个SPORE资助期证明了NIS基因转移在体外和体内的可行性， 一项I期临床试验将很快开始，这项新的基因靶向放射治疗的男性局部 复发性前列腺癌。更新提案中概述的实验将1）完成第一阶段试验 并检查其结果; 2）将第二代腺病毒进行临床试验， 驱动NIS表达的probasin启动子是高度前列腺特异性的;和3）开发复制型腺病毒 表达NIS的载体将提供对前列腺癌的更高功效和特异性，以及 全身给药后活性增加，从而靶向转移性疾病。这些研究将 目的：研究NIS基因转移作为治疗转移性前列腺癌的方法的潜力。 这是第一个这样描述的疾病。此外，在我们的实验室中成功地演示了放射性碘效应， 前列腺癌模型将有助于激发对NIS作为其他癌症治疗基因的兴趣 类型