Enhancing Viral Oncolysis with Vasculostatin Gene Delivery

通过血管抑素基因传递增强病毒溶瘤作用

基本信息

批准号：
8450666
负责人：
Balveen Kaur
金额：
$ 38万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8450666
关键词：
American Cancer Society Angiogenesis Inhibitors Angiostatic Proteins Animal Model Apoptotic Binding Biology Brain Brain Neoplasms Cells Cessation of life Clinical Trials Cytolysis Development Dominant-Negative Mutation Eating Extracellular Domain Gene Delivery Gene Expression Genes Glioma Goals Grant Herpesvirus 1 Hypoxia In Vitro Laboratories Lead Length Malignant Glioma Malignant Neoplasms Modality Mus Oncolytic Oncolytic viruses Patients Perfusion Phagocytosis Phosphatidylserines Play Property Research Role Signal Transduction Simplexvirus Structure Testing Therapeutic Tissues Toxic effect Translating Tumor Biology Vasculostatin Viral Virus Virus Replication angiogenesis arm base cancer cell density expectation extracellular foot in vivo killings macrophage nestin protein oncolysis outcome forecast preclinical toxicity public health relevance receptor response tumor tumor microenvironment tumorigenic

项目摘要

DESCRIPTION (provided by applicant): The ultimate goal of this proposal is to understand the contribution of Vstat120 expressing oncolytic viruses on OV propagation, tumor biology and anti-tumor efficacy. These results will lead to a better understanding of OV therapy induced changes in tumor biology and will lead to the development of a dually armed cancer killing OV. The OV treatment of tumors relies on cancer-specific replication of the virus leading to tumor destruction with minimal toxicity to adjacent non-neoplastic tissue. Results from six clinical trials using replication competent OVs to treat patients with malignant glioma have shown the new modality to be relatively safe, but high expectations of efficacy remain unmet (1, 2). The tumor's microenvironment is increasingly recognized as an important determinant for its progression and its response to therapeutics. My laboratory has recently created two oncolytic viruses, armed with an anti-angiogenic gene. We now propose to elucidate the role of this angiostatic protein in viral propagation, glioma biology and OV efficacy.

描述（由申请人提供）：该提案的最终目标是了解VSTAT120表达溶瘤病毒对OV传播，肿瘤生物学和抗肿瘤功效的贡献。这些结果将使对OV疗法诱发的肿瘤生物学变化有更好的了解，并导致双手武装癌症杀死OV的发展。肿瘤的OV治疗依赖于该病毒的癌症特异性复制，导致肿瘤破坏，对邻近非肿瘤组织的毒性最小。六项临床试验的结果使用复制能干的OV治疗恶性神经胶质瘤患者的结果表明，新的方式相对安全，但对疗效的高期望仍然尚未得到满足（1，2）。肿瘤的微环境越来越被认为是其进展的重要决定因素及其对治疗剂的反应。我的实验室最近创建了两种具有抗血管生成基因的溶瘤病毒。现在，我们建议阐明这种血管抑制蛋白在病毒传播，神经胶质瘤生物学和OV疗效中的作用。