ULTRASOUND ENHANCEMENT OF CANCER GENE THERAPY

超声波增强癌症基因治疗

• 批准号: 6489329
• 负责人: DOUGLAS LAWRENCE MILLER
• 金额: $ 24.34万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-10 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6489329
• 关键词: contrast media; disease /disorder model; gene therapy; hemorrhage; iatrogenic disease; interleukin 12; laboratory mouse; laboratory rabbit; melanoma; metastasis; method development; neoplasm /cancer therapy; nonhuman therapy evaluation; outcomes research; patient monitoring device; plasmids; ultrasound; ultrasound therapy

The possibility of using ultrasound to enhance cancer gene therapy will be evaluated. Preliminary research has demonstrated that ultrasound interacting with gas bubbles in tissue can induce some cells which avoid lysis to take up large molecules, such as DNA vectors, and that these cells can survive to express gene products. Application of this phenomenon to can gene therapy should avoid use of viral vectors, allow transfection of multiple large plasmids, focus treatment on the tumor target, and combine massive tumor ablation with high efficiency transfection of survival cells. Another favorable consideration is that needed ultrasound equipment, including shockwave generation systems for lithotripsy, is already available in most large medical centers. Three specific aims are: already available in most large medical centers. Three specific aims are: (1) to experiment with the delivery of DNA plasmids and gas bubbles to tumors for optimizations of the tumor ablation and transfection-enhancement processes, (2) to demonstrate cancer gene therapy with plasmids of established therapeutic value, such as are being developed for immunotherapy, in different mouse tumor models and (3) to develop the ultrasound enhancement protocol including ultrasound guidance of injection, variation of ultrasound parameters, treatment monitoring by acoustic cavitation emissions, and imaging of tumors for complete treatment coverage. Finally, the method will be matched and oriented for application to difficult clinical situations which require new approaches to successful management. This research will provide a bridge from the basic research breakthrough to specific therapeutic applications and urgently needed clinical research programs utilizing this novel technology.

将评估使用超声增强癌症基因治疗的可能性。初步研究表明，超声与组织中的气泡相互作用可以诱导一些避免裂解的细胞摄取大分子，如DNA载体，并且这些细胞可以存活以表达基因产物。将这种现象应用于can基因治疗应避免使用病毒载体，允许多个大质粒的转染，将治疗集中在肿瘤靶点上，并将大规模肿瘤消融与存活细胞的高效转染相结合。另一个有利的考虑是，所需的超声设备，包括碎石术的冲击波发生系统，已经在大多数大型医疗中心。三个具体的目标是：已经在大多数大型医疗中心提供。三个具体目标是：（1）试验将DNA质粒和气泡递送至肿瘤以优化肿瘤消融和转染增强过程，（2）在不同的小鼠肿瘤模型中证明用具有确定治疗价值的质粒进行癌症基因治疗，例如正在开发用于免疫治疗的质粒，和（3）开发超声增强方案，包括超声引导注射，超声参数的变化、通过声空化发射的治疗监测以及用于完全治疗覆盖的肿瘤成像。最后，该方法将被匹配和定向应用于困难的临床情况，需要新的方法来成功的管理。这项研究将提供一个桥梁，从基础研究的突破，具体的治疗应用和迫切需要的临床研究计划，利用这一新技术。

项目成果

Sonoporation: Mechanical DNA delivery by ultrasonic cavitation.

• DOI: 10.1023/a:1022983907223
• 发表时间: 2002-11-01
• 期刊: Somatic Cell and Molecular Genetics
• 作者: Miller, Douglas L.;Pislaru, Sorin V.;Greenleaf, James F.
• 通讯作者: Greenleaf, James F.

Combined shock-wave and immunogene therapy of mouse melanoma and renal carcinoma tumors.

小鼠黑色素瘤和肾癌肿瘤的冲击波和免疫基因联合治疗。

• DOI: 10.1016/s0301-5629(02)00536-7
• 发表时间: 2002
• 期刊: Ultrasound in medicine & biology
• 影响因子: 2.9
• 作者: Song,Jianming;Tata,Darrell;Li,Lang;Taylor,Jeremy;Bao,Shiping;Miller,DouglasL
• 通讯作者: Miller,DouglasL