Image-guided Gene and Virotherapy for Pancreatic Cancer

图像引导胰腺癌基因和病毒治疗

• 批准号: 7066599
• 负责人: STEPHANIE KAY CARLSON
• 金额: $ 13.12万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7066599
• 关键词: adenocarcinoma; attenuated microorganism; bioimaging /biomedical imaging; biotechnology; combination cancer therapy; gene delivery system; gene expression; gene therapy; histopathology; image guided surgery /therapy; iodine; laboratory mouse; measles virus; neoplasm /cancer radionuclide therapy; nonhuman therapy evaluation; pancreas imaging /visualization; pancreas neoplasms; radionuclide imaging /scanning; radiotracer; single photon emission computed tomography; therapy design /development; transfection /expression vector; xenotransplantation

DESCRIPTION (provided by applicant): Pancreatic adenocarcinoma is one (1) of the most lethal cancers in the United States, with an average survival of 3 to 6 months from the time of diagnosis. Currently available treatments have had little impact on the course of the disease. The goal of this research plan is to incorporate molecular imaging and image-guided interventional techniques to develop a new approach for the treatment of pancreatic cancer by using intratumoral injection of an attenuated measles virus (MV-Edm) genetically modified with the sodium-iodide symporter (NIS) gene (MV-NIS). MV-Edm was chosen for these studies because 1) MV-Edm infection causes massive cell-cell fusion, leading to a potent oncolytic effect in multiple human tumor models, and 2) NIS gene expression allows radioiodine-based in vivo imaging and therapy strategies. The propensity for local tumor invasion makes pancreatic cancer a compelling target for intratumoral gene delivery, owing to the potential value of local therapy. Our overall hypothesis is that image-guided intratumoral MV-NIS therapy combined with in vivo imaging of gene expression and therapeutic response will facilitate the development of genetically based therapies for pancreatic cancer. The specific aims are to 1) determine the sensitivity and resolution of radioiodine-based imaging techniques for in vivo monitoring of MV-NIS infection and gene expression in pancreatic cancer xenografts, 2) use these imaging techniques to determine the efficiency and enhance the uniformity of intratumoral MV-NIS delivery, and 3) determine the utility of NIS as a therapuetic transgene for 131 l radiovirotherapy. The proposed career development plan combines didactic course work in molecular medicine and gene therapy with a supervised laboratory-based research experience. The long-term goals are to 1) develop an independent laboratory-based and translational research career in image-guided cancer gene therapy, and 2) translate the results of our laboratory research into appropriate clinical trials and therapeutic strategies for patients who have locally advanced or metastatic pancreatic carcinoma.

描述（由申请人提供）：胰腺腺癌是美国最致命的癌症中的一（1），自诊断之时的平均存活率为3至6个月。目前可用的治疗对疾病的影响很小。该研究计划的目的是结合分子成像和图像引导的介入技术，以使用肿瘤内注射肿瘤的麻疹病毒（MV-EDM）遗传改性的钠 - 碘（Nis）基因（NIS）基因（MV-NIS（MV-NIS））。选择这些研究的MV-EDM是因为1）MV-EDM感染会引起大量细胞 - 细胞融合，从而在多个人类肿瘤模型中产生有效的溶瘤作用，而2）NIS基因表达允许基于放射性碘的体内成像和治疗策略。局部肿瘤侵袭的倾向使胰腺癌 由于局部治疗的潜在值，这是肿瘤内基因递送的引人注目的目标。我们的总体假设是，图像引导的肿瘤内MV-NIS疗法结合基因表达和治疗反应的体内成像将有助于开发基于遗传性的胰腺癌疗法。具体目的是1）确定基于放射性碘的成像技术的敏感性和分辨率，用于体内监测MV-NIS感染和基因表达中胰腺癌异种移植物中的基因表达，2）使用这些成像技术来确定效率并增强效率，并提高MV-NIS递送的均匀性，并确定NIS的统一性，并确定NIS的效率。放射疗法。拟议的职业发展计划将分子医学和基因治疗方面的教学课程与受监督的基于实验室的研究经验相结合。长期目标 1）在图像引导的癌症基因治疗方面开发了独立的基于实验室的转化研究职业，以及2）将我们的实验室研究结果转化为适当的临床试验和治疗策略，并为患有局部高级或转移性胰腺癌的患者进行了治疗策略。