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Therapeutic Potential of IL-15 Plasmid Delivery to Tumors Using Electroporation

使用电穿孔将 IL-15 质粒递送至肿瘤的治疗潜力

基本信息

批准号：
8444689
负责人：
RICHARD HELLER
金额：
$ 24.55万
依托单位：
OLD DOMINION UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8444689
关键词：
Adverse effects Animal Model Animals Antitumor Response Biological Cells Clinic Clinical Clinical Research Code Cutaneous Data Development Disabled Persons Disease Dose Effectiveness Electroporation Evaluation Experimental Models Gene Transfer Genes Genome Goals Growth Health Status Immune Immune response Immune system Immunotherapy Injection of therapeutic agent Interleukin-15 Intramuscular Lead Lesion Liver Local Therapy Localized Lesion Lung Malignant Neoplasms Mediating Melanoma Cell Memory Metastatic Melanoma Methods Mus Muscle Myomatous neoplasm Neoplasm Metastasis Normal tissue morphology Organ Outcome Pattern Plasmids Population Prevention Principal Investigator Protocols documentation Recombinant Proteins Recurrence Research Research Proposals Role Safety Serum Skin Solid Neoplasm Staging Subcutaneous Injections System T-Lymphocyte Tail Testing Therapeutic Therapeutic Agents Time Tissues Toxic effect Translating Treatment Efficacy Treatment Protocols Vaccines Veins Work base chemotherapeutic agent cytokine design fighting gene therapy handicapping condition immunogenicity improved in vivo melanoma neoplastic cell non-viral gene delivery plasmid DNA pre-clinical prevent programs public health relevance response subcutaneous tumor tumor growth vector

项目摘要

DESCRIPTION (provided by applicant): The long range goal of our research program is the development of delivery systems that will be effective for a variety of cancers. The major focus of these studies is to examine the use of non-viral gene transfer approach that can be used for immunotherapy protocols and its potential as a treatment of solid tumors. In vivo electroporation has shown a great deal of promise as a means of enhancing the expression of plasmid DNA in a variety of tissues including muscle, tumor, skin and liver. Previously, in vivo electroporation has been shown to be an effective way to enhance the effectiveness of chemotherapeutic agents in both pre-clinical and clinical studies. More recently, several studies have shown that delivering a plasmid coding for a cytokine in combination with electroporation can elicit an anti-tumor response. The specific research proposed in this application is intended to determine if the using in vivo electroporation to deliver a plasmid DNA coding for the cytokine IL-15 can be effective in treating metastatic melanoma. The study will be designed to accomplish the following specific aims: i. to evaluate B16.F10 melanoma growth or regression in response to electrically mediated IL-15 plasmid delivery. ii. To determine tumor and serum immune responses elicited after electrically mediated IL-15 plasmid delivery. iii. To evaluate the effect of intratumoral and intramuscular electrically mediated IL-15 plasmid delivery on the growth of metastatic melanomas, including both subcutaneous and lung lesions. iv. To evaluate the potential toxicity of electrically mediated IL-15 plasmid delivery for the treatment of melanoma. Successful completion of this project will demonstrate the potential role of IL-15 gene therapy delivered as a plasmid by electroporation as a therapy for melanoma.

描述（由申请人提供）：我们研究计划的长期目标是开发对各种癌症有效的递送系统。这些研究的主要重点是检查可用于免疫治疗方案的非病毒基因转移方法的使用及其作为实体瘤治疗的潜力。体内电穿孔作为一种增强质粒DNA在包括肌肉、肿瘤、皮肤和肝脏在内的多种组织中表达的手段已经显示出很大的前景。以前，体内电穿孔已被证明是在临床前和临床研究中增强化疗剂有效性的有效方法。最近，几项研究表明，递送编码细胞因子的质粒与电穿孔组合可以引发抗肿瘤应答。本申请中提出的具体研究旨在确定使用体内电穿孔递送编码细胞因子IL-15的质粒DNA是否可有效治疗转移性黑素瘤。这项研究旨在实现以下具体目标：评价电介导的IL-15质粒递送对B16.F10黑素瘤生长或消退的响应。二.确定电介导的IL-15质粒递送后引发的肿瘤和血清免疫应答。三.评价肿瘤内和肌内电介导的IL-15质粒递送对转移性黑色素瘤（包括皮下和肺部病变）生长的影响。四.评价电介导IL-15质粒递送治疗黑色素瘤的潜在毒性。该项目的成功完成将证明IL-15基因治疗作为黑色素瘤治疗的潜在作用，通过电穿孔作为质粒递送。