Complementary Adenoviral Vectors for Treatment of Cancer

用于治疗癌症的互补腺病毒载体

• 批准号: 6946933
• 负责人: ROBERT E SOBOL
• 金额: $ 76.75万
• 依托单位: MAGNUM THERAPEUTICS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-07 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6946933
• 关键词: Adenoviridae; Macaca fascicularis; alpha fetoprotein; clinical research; clinical trial phase I; cytokine; gene expression; gene therapy; histopathology; human subject; human therapy evaluation; interleukin 3; laboratory mouse; neoplasm /cancer immunotherapy; patient oriented research; polymerase chain reaction; prostate neoplasms; prostate specific antigen; prostate surgery; radiosensitizer; technology /technique development; transfection /expression vector; tumor antigens; virus replication

DESCRIPTION (provided by applicant) The major goal of this proposal is to determine the therapeutic potential of a replication conditional adenovirus vector, DuaI-AdlL-3. This vector system is composed of two transcomplementing adenoviruses that permit selective replication in the prostate and prostate tumors. It is designed to engender a multimodal therapeutic response by establishing a lytic infection in prostate tumor cells by enhancing the tumoricidal effects of radiation therapy and by enhancing the immune response to endogenous tumor antigens. The genome of one of the viral components, Max-AdlL-3, contains the adenoviral-inverted terminal repeats for replication, the adenoviral packaging signal, the E1 genes with E1A under the control of a prostate specific antigen (PSA) promoter, and an IL-3 expression cassette. This vector propagates only in cells that express PSA when the helper adenoviral vector is also present. In animal tumor models, the combination of IL-3 cytokine gene therapy with radiotherapy was synergistic, resulting in enhanced efficacy of local radiotherapy and systemic anti-tumor immunity. In the preclinical studies of the Phase I SBIR grant we have shown our DuaI-AdlL-3 oncolytic vector system exhibits the oncolytic, immunity enhancing, and radiation-enhancing properties incorporated into the vector. This Phase II proposal will extend this project to clinical application.

描述（由申请人提供）