Optimizing oncolytic virus therapy for glioblastoma

优化胶质母细胞瘤的溶瘤病毒治疗

基本信息

批准号：
10618742
负责人：
Balveen Kaur
金额：
$ 38.5万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10618742
关键词：
Adult Glioblastoma Angiogenesis Inhibitors Biodistribution Biological Response Modifier Therapy Brain Brain Neoplasms Cells Decision Trees Excision FDA approved Future G207 Genes Glioblastoma Glioma Goals Granulocyte-Macrophage Colony-Stimulating Factor Herpesvirus 1 Immunocompetent In Vitro Intracranial Neoplasms Laboratories Lead Lipids Lytic Malignant Neoplasms Metastatic Melanoma Mitochondria Mus Oncolytic Oncolytic viruses PTEN gene Patients Phase Phosphoric Monoester Hydrolases Pre-Clinical Model Production Prognosis Proteins Public Health Reading Frames Reporting Resistance Safety Simplexvirus Structure Testing Therapeutic Toxic effect Transgenes Treatment Efficacy Vertebral column Viral Virus anti-tumor immune response antitumor effect attenuation clinical development cytotoxicity extracellular improved in vivo melanoma neoplastic cell neurovirulence novel novel strategies novel therapeutics oncolytic virotherapy prototype reconstitution therapeutic development therapeutic evaluation therapeutic transgene tumor tumorigenic vector virus development

项目摘要

ABSTRACT The overarching goal of this project is to identify a new lead oncolytic virus for the treatment of adult glioblastoma (GBM). Oncolytic viral (OV) therapy is a promising biological therapy that preferentially targets tumor cells for lytic destruction [1, 2]. Oncolytic HSV-1 (oHSV) derived virus that encodes for GM-CSF (IMLYGIC®) has been recently approved for non-ressectable metastatic melanoma [3, 4]. In our past endeavors, we have created and tested the therapeutic efficacy of oHSV armed with therapeutic transgenes. These viruses have been created in rHSVQ1 (HSVQ): an HSV virus backbone that is deleted for both copies of the viral neuro- virulence gene ICP34.5 and it contains a gene disrupting insertion in viral ICP6. This backbone has attenuations identical to G207, a virus that has been tested and found to be safe in patients with GBM after intracranial inoculation into the tumor or when given into the post resection tumor cavity [5, 7-10]. Here we will create a novel dually armed oncolytic virus (that encode for therapeutic transgenes: Vstat120, PTENα or both) and then compare the dually armed and single transgene armed viruses to identify an optimal vector for future IND guided studies.

抽象的该项目的总体目标是确定一种新的溶瘤病毒以治疗成人胶质母细胞瘤（GBM）。溶瘤病毒（OV）疗法是一种有前途的生物学疗法，优先针对目标肿瘤细胞用于裂解的破坏[1，2]。溶瘤HSV-1（OHSV）衍生的病毒，该病毒编码为GM-CSF （Imlygic®）最近已批准用于不可压缩的转移性黑色素瘤[3，4]。在我们过去的努力中，我们已经创建并测试了具有治疗翻译的OHSV的治疗效率。这些病毒已在RHSVQ1（HSVQ）中创建：一种HSV病毒骨架，该主链被删除，用于两种病毒神经的副本毒力基因icp34.5及其包含一个破坏病毒ICP6中插入的基因。这个骨干有衰减与G207相同，G207已经过测试并在颅内后GBM患者中被发现安全接种到肿瘤中，或分入切除后肿瘤腔[5，7-10]。在这里，我们将创作一本小说双武装癌性病毒（为热转基因编码：VSTAT120，PTENα或两者），然后比较双武装和单一转型武装病毒，以识别未来IND指导的最佳向量研究。