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Using genetically engineered mouse models of brain tumors to develop therapeutic nanoparticles & biomaterials

使用基因工程小鼠脑肿瘤模型开发治疗性纳米颗粒

基本信息

批准号：
9194397
负责人：
ERIC C. HOLLAND
金额：
$ 64.48万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-11 至 2018-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9194397
关键词：
Antigen-Antibody Complex Applications Grants Area Automobile Driving Beds Biocompatible Materials Biopolymers Brain Brain Neoplasms Cell Count Cells Clinical CpG Island Methylator Phenotype Cytotoxic Chemotherapy Devices Disease Effectiveness Ependymoma Genetically Engineered Mouse Glioblastoma Glioma Grant Hematopoietic Neoplasms Human Imaging technology Immune Immune system Immunity Immunologic Adjuvants Immunosuppressive Agents Immunotherapy In Situ Injectable Injection of therapeutic agent Intervention Investigation Knowledge Lymphocyte Methods Modeling Mus Mutation Operative Surgical Procedures Patients Pharmaceutical Preparations Phenotype Polymers Radiation Radiation therapy Recurrence Relapse Reporting Resistance Suggestion Surgical Oncology System T cell therapy T-Lymphocyte Technology Testing Therapeutic Therapeutic Effect Therapeutic Intervention Time Translating Treatment Failure Vaccines Work base brain tumor resection cancer type cell type chemotherapy design effective therapy human data improved killings melanoma molecular subtypes mouse model mutant nanoparticle neoplastic cell public health relevance radiation resistance radiation response success synergism trafficking tumor tumor microenvironment

项目摘要

DESCRIPTION (provided by applicant): We have developed a suite of genetically-engineered mouse models of human gliomas and ependymomas that we have used to inform treatment options for clinical agents. High-grade gliomas are fatal in nearly all cases because of the inability to fully resect them, and the resistance of the remaining tumors cells to available therapy. There are two main molecular subtypes of glioma, those less aggressive tumors with IDH1 mutation and a methylator phenotype designated CIMP, and the more aggressive non-CIMP gliomas that are frequently grade 4 GBMs. The treatment of these tumors is surgery followed by radiation and chemotherapy for high-grade gliomas, with almost uniform recurrence and a median survival of less than 2 years. We clearly need improved strategies for treating these brain tumors, partly by enhancing radiation therapy and partly by getting the immune system to work better at attacking these tumor cells. In this grant we will develop these methods in mice via nanoparticles and biopolymers. This grant application is an opportunity to gather a team of leading experts in these fields to use GEMM models of these tumor types to advance these areas. In each case we will be developing technology in these models that can be translated to human trials within a few years.

描述（由申请人提供）：我们已经开发了一套人类神经胶质瘤和室管膜瘤的基因工程小鼠模型，我们已用于告知临床药物的治疗选择。高级别胶质瘤在几乎所有情况下都是致命的，因为无法完全切除它们，并且剩余的肿瘤细胞对可用的治疗具有抗性。胶质瘤有两种主要的分子亚型，即具有IDH 1突变和甲基化表型（称为CIMP）的侵袭性较低的肿瘤，以及侵袭性较高的非CIMP胶质瘤（通常为4级GBM）。这些肿瘤的治疗方法是手术，然后对高级别胶质瘤进行放疗和化疗，复发率几乎一致，中位生存期不到2年。我们显然需要改进治疗这些脑肿瘤的策略，部分是通过加强放射治疗，部分是通过让免疫系统更好地攻击这些肿瘤细胞。在这项资助中，我们将通过纳米颗粒和生物聚合物在小鼠中开发这些方法。这项资助申请是一个机会，可以聚集这些领域的领先专家团队，使用这些肿瘤类型的GEMM模型来推进这些领域。在每种情况下，我们都将在这些模型中开发技术，这些技术可以在几年内转化为人体试验。