ULTRASOUND ENHANCEMENT OF CANCER GENE THERAPY

超声波增强癌症基因治疗

• 批准号: 6342188
• 负责人: DOUGLAS LAWRENCE MILLER
• 金额: $ 24.3万
• 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/6342188
• 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.

将评估利用超声波加强癌症基因治疗的可能性。初步研究表明，超声与组织内气泡的相互作用可以诱导一些避免溶解的细胞吸收大分子，如DNA载体，这些细胞可以存活并表达基因产物。将这一现象应用于can基因治疗应避免使用病毒载体，允许转染多个大质粒，集中治疗肿瘤靶点，将大量肿瘤消融与高效转染存活细胞相结合。另一个有利的考虑是所需的超声设备，包括用于碎石术的冲击波产生系统，在大多数大型医疗中心已经可用。有三个具体目标：在大多数大型医疗中心已经可以使用。三个具体目标是：(1)实验将DNA质粒和气泡输送到肿瘤中，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展示具有治疗价值的质粒对癌症的基因治疗，例如正在开发用于免疫治疗的质粒；(3)开发超声增强方案，包括超声引导注射，超声参数的变化，以及超声辅助治疗。通过声空化发射进行治疗监测，并对肿瘤进行成像，以实现完整的治疗覆盖。最后，该方法将匹配和面向应用于困难的临床情况，需要新的方法来成功管理。这项研究将为利用这项新技术从基础研究突破到特定治疗应用和迫切需要的临床研究项目提供一座桥梁。