Targeted Adenoviral Gene Therapy for Malignant Glioma

恶性胶质瘤的靶向腺病毒基因治疗

• 批准号: 7236585
• 负责人: MACIEJ S LESNIAK
• 金额: $ 16.51万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7236585
• 关键词: Adenovirus Vector; Adenoviruses; Adult; Binding Sites; Biomedical Research; Brain Neoplasms; CAR receptor; Cells; Clinical; Clinical Trials; Data; Dose; Education; Exhibits; Fiber; Funding; Future; Gene Delivery; Generations; Genes; Glioblastoma; Glioma; Goals; Grant; Hospitals; Immune; Immune Targeting; Immune response; Integrins; Lead; Malignant Glioma; Malignant Neoplasms; Malignant neoplasm of brain; Modality; Mutation; Neuraxis; Neurosurgical Procedures; Normal Cell; Oncolytic; Operative Surgical Procedures; Organ; Patients; Peptides; Predisposition; Principal Investigator; Publications; Purpose; Radiation therapy; Relative (related person); Research; Research Personnel; Residencies; Resistance; Solid; Specificity; Testing; Time; Tissues; Toxic effect; Translating; Tropism; United States National Institutes of Health; Viral Vector; Virus; base; cancer therapy; day; design; gene therapy; in vivo; integrin beta5; neoplastic cell; neurosurgery; pre-clinical; professor; receptor; research study; success; tumor; vector

DESCRIPTION (provided by applicant): High grade gliomas represent the most common primary malignant tumor of the adult central nervous system. Unfortunately, the median survival after surgical intervention alone is only six months and the addition of radiotherapy can extend this time to only nine months. Consequently, efforts aimed at developing new therapies have focused on new treatment strategies that specifically target tumor cells and spare normal cells. One such modality, gene therapy, has shown promise in the spectrum of agents utilized against brain tumors. The success of gene therapy depends on efficient gene delivery into target cells. Viral vectors, in the form of adenoviruses, have provided one potential means for the delivery of gene therapy. Several studies, however, have demonstrated a relative resistance of brain tumors to adenoviral vectors, a finding that was subsequently attributed to the quantitative deficiency of the primary adenoviral receptor, the Coxsackie Adenovirus Receptor (CAR), on tumor cells. The main purpose of this project is to develop re-targeted adenoviral vectors with the capacity to enhance immune based cancer therapies. The focus of the re-targeting has been the expression of alpha-v-beta3 and alpha-v-beta5 on many solid organ tumors. This project aims to develop second generation adenoviruses with altered tropism for alpha-v-beta3 and alpha-v-beta5 integrins in order to achieve cell-specific targeting of immune-modulatory genes. The principal investigator, Dr. Maciej S. Lesniak, has recently completed his residency in neurological surgery and is currently as Assistant Professor of Neurosurgery at the Johns Hopkins Hospital. Dr. Lesniak immediate goals are to establish a solid research background that will allow him to become an independent investigator. By undertaking this project and furthering his scientific and biomedical research education, Dr. Lesniak hopes to one day translate this research to the clinical setting and the treatment of patients with malignant brain tumors.

描述（由申请人提供）： 高级神经胶质瘤是成人中枢神经系统最常见的原发性恶性肿瘤。不幸的是，仅手术干预后的中位生存期只有六个月，而放射疗法的增加可以延长至9个月。因此，旨在开发新疗法的努力集中在专门针对肿瘤细胞和备用正常细胞的新治疗策略上。一种这种方式，一种基因疗法，在用于针对脑肿瘤的药物谱中显示出了希望。基因治疗的成功取决于有效的基因递送到靶细胞中。病毒载体以腺病毒的形式提供了一种潜在的基因治疗方法。然而，几项研究表明，脑肿瘤对腺病毒载体的相对耐药性，这一发现随后归因于肿瘤细胞上原代腺病毒受体的定量缺乏，coxsackie腺病毒受体（CAR）。该项目的主要目的是开发重新定位的腺病毒载体，具有增强免疫癌症疗法的能力。重新定位的重点是α-V-Beta3和alpha-V-Beta5在许多实体器官肿瘤上的表达。该项目旨在开发第二代腺病毒，其α-V-BetA3和alpha-V-Beta5整合素的向量改变，以实现免疫调节基因的细胞特异性靶向。首席研究员Maciej S. Lesniak博士最近完成了他在神经外科手术中的居留权，目前是约翰·霍普金斯医院的神经外科助理教授。莱斯尼亚克（Lesniak）博士的立即目标是建立可靠的研究背景，使他成为独立的研究者。通过进行这项项目并促进他的科学和生物医学研究教育，Lesniak博士希望有一天将这项研究转化为临床环境和对恶性脑肿瘤患者的治疗。