TNF-related apoptosis-inducing ligan (TRAIL) gene therapy for prostate cancer

TNF 相关凋亡诱导配体 (TRAIL) 基因疗法治疗前列腺癌

• 批准号: 7244072
• 负责人: Richard Dwayne Williams
• 金额: $ 12.3万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-19 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7244072
• 关键词: Absorbable Gelatin Sponge; Affect; Apoptosis; Apoptotic; Cessation of life; Collagen; Cytotoxic agent; Development; Effectiveness; Future; Gene Delivery; Gene Transfer; Immune; Immunity; Injection of therapeutic agent; Ligands; Localized; Malignant neoplasm of prostate; Mediating; Methods; Operative Surgical Procedures; Patients; Phase I Clinical Trials; Prostate; Prostate Cancer therapy; Prostatic; Prostatic Neoplasms; Proteins; Radiation therapy; Regional Disease; Research Design; Technology; Toxic effect; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Viral; base; cancer cell; cytotoxic; gene delivery system; gene therapy; human TNF protein; neoplastic cell; novel therapeutics

DESCRIPTION (provided by applicant): Definitive treatment of prostate cancer is limited to radical surgery or radiation therapy for localized or regional disease. Gene transfer technology offers the potential for the development of new therapies for prostate cancer. The proposed project will employ the unique apoptotic agent, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and a collagen-based matrix that enhances gene delivery system to augment immune activation. Objective/hypothesis: The long-term objective of the project is to develop an effective treatment for prostate cancer. Specifically, treatment involves the viral-mediated transfer of the gene for the cytotoxic protein TRAIL into the prostate, resulting in prostate tumor cell apoptotic death and activation of systemic antitumor immunity. Specific Aims: (1) Determine the local and systemic toxicity associated with intraprostatic injection of Ad5-TRAIL delivered in Gelfoam. (2) Examine the distribution of Ad5-TRAIL within the human prostate after transperineal injection and determine the effect of transperineal injection of Ad5-TRAIL on existent prostate cancer. Study Design: The primary focus of this proposal is to conduct a phase I clinical trial using intra-prostatic injection of Ad5-TRAIL in patients with clinically localized prostate cancer. The injections will be administered in a collagen matrix (Gelfoam) which we expect will enhance delivery and distribution. The local and systemic toxicity associated with intraprostatic injection of Ad5-TRAIL will also be determined. TRAIL is an effective cytotoxic agent which affects only prostate cancer cells. The proposed studies will help develop methods to maximize gene delivery and determine the toxicity and effectiveness of localized gene transfer therapy which could provide the basis for future studies leading to a new therapeutic approach for prostate cancer.

描述（由申请人提供）：前列腺癌的连续治疗仅限于根治性手术或局部或区域性疾病的放射治疗。基因转移技术为前列腺癌新疗法的开发提供了潜力。拟议的项目将采用独特的凋亡剂，肿瘤坏死因子相关的凋亡诱导配体（TRAIL）和胶原基基质，增强基因传递系统，以增强免疫激活。目标/假设：该项目的长期目标是开发一种有效的前列腺癌治疗方法。具体而言，治疗涉及病毒介导的细胞毒性蛋白质TRAIL的基因转移到前列腺中，导致前列腺肿瘤细胞凋亡死亡和全身抗肿瘤免疫的激活。具体目的：（1）确定与前列腺内注射明胶海绵中递送的Ad 5-TRAIL相关的局部和全身毒性。(2)经会阴注射Ad 5-TRAIL后，检测Ad 5-TRAIL在人前列腺内的分布，并确定经会阴注射Ad 5-TRAIL对现存前列腺癌的影响。研究设计：该提案的主要重点是在临床局限性前列腺癌患者中使用前列腺内注射Ad 5-TRAIL进行I期临床试验。注射将在胶原蛋白基质（Gelfoam）中进行，我们预计这将增强递送和分布。还将确定与前列腺内注射Ad 5-TRAIL相关的局部和全身毒性。TRAIL是一种有效的细胞毒性剂，仅影响前列腺癌细胞。拟议的研究将有助于开发最大化基因递送的方法，并确定局部基因转移治疗的毒性和有效性，这可能为未来研究前列腺癌的新治疗方法提供基础。