Novel Cell Delivery Method for Brain Tumor Therapy

用于脑肿瘤治疗的新型细胞递送方法

基本信息

批准号：
8637349
负责人：
Behnam Badie
金额：
$ 18.4万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8637349
关键词：
Alternative Therapies Animal Experiments Animals Antineoplastic Agents Aspirate substance Blood - brain barrier anatomy Blood coagulation Brain Brain Mass Brain Neoplasms Cannulas Cattle Cauterization - action Cauterize Cell Therapy Cells Clinical Clinical Trials Development Device or Instrument Development Devices Disease Disease Progression Family suidae Feasibility Studies Formalin Gelatin Generations Glioblastoma Glioma Goals Hematoma Hemostatic function Human Image In Vitro Infusion procedures Injection of therapeutic agent Injury Laboratories Liver Malignant Neoplasms Malignant neoplasm of brain Mechanics Methods Mission Modeling Natural Killer Cells Neoplasm Metastasis Neuraxis Operative Surgical Procedures Organ Patients Performance Pharmaceutical Preparations Preparation Public Health Safety Solid Techniques Testing Therapeutic Thermal Ablation Therapy Time Tissues Trephine hole Tumor Debulking Tumor Tissue Viral Vector cancer therapy cranium design frontal lobe improved in vitro testing in vivo innovation instrument macromolecule member minimally invasive neoplastic cell neurosurgery novel pre-clinical prevent prototype public health relevance tumor

项目摘要

DESCRIPTION (provided by applicant): Even when treated with aggressively with current therapies, most patients with primary malignant brain tumors (glioma) survive less than two years. Although targeted therapies are being developed, the blood-brain barrier prevents large molecules from penetrating the central nervous system and moving to the brain. Because gliomas rarely metastasize, a localized tumor treatment could be sufficient to prevent the disease from progressing. As a result, methods are being developed to allow for the delivery of tumor-specific macromolecules directly into the brain tumors. However, these approaches require infusions of high-volumes of drugs which can be time consuming or impractical in an organ with limited space capacity, such as the brain. Thus, there is a pressing need for improved methods to deliver targeted macromolecules into brain tumors. The goal of this project is to fabricate and evaluate the feasibility of a novel instrument that is capable of creating a cavity within brain tumors using image-guided, minimally invasive techniques. The cavity that is generated by the instrument can then be used as a reservoir to deliver anti-cancer macromolecules or cells directly into the tumor. Using image guidance, the instrument is inserted into the tumor through a small burr hole for central tumor debulking. The unique mechanical features of this instrument will allow it to detach, fragment, cauterize and aspirate the tumor tissue through a small channel. Initial studies using proof-of concept prototypes have demonstrated the mechanical feasibility of this approach. Here, we propose to fabricate prototypes of a pre-clinical grade device, and characterize the performance of this instrument in vitro and in vivo. After completing this project, we expect to generate instrument designs for fabricating clinical- grade prototypes that are suitable for testing in human safety trials.

描述（由申请人提供）：即使使用当前疗法进行积极治疗，大多数原发性恶性脑肿瘤（神经胶质瘤）的患者的生存不到两年。尽管正在开发靶向疗法，但血脑屏障可以防止大分子穿透中枢神经系统并移至大脑。由于神经胶质瘤很少转移，因此局部肿瘤治疗可能足以防止疾病发展。结果，正在开发方法以允许将肿瘤特异性大分子直接递送到脑肿瘤中。但是，这些方法需要大量的大量药物输注，这些药物可能在有限的空间容量（例如大脑）的器官中耗时或不切实际。因此，迫切需要改进的方法将靶向大分子输送到脑肿瘤中。该项目的目的是制造和评估一种能够使用图像引导的，微创的技术在脑肿瘤中创建腔的新型仪器的可行性。然后，仪器产生的腔可以用作将抗癌大分子或细胞直接输送到肿瘤中的储层。使用图像引导，将仪器通过一个小毛刺孔插入肿瘤中，以缓解中央肿瘤。该仪器的独特机械特征将使其能够通过小通道脱离，碎片，烧毁并吸入肿瘤组织。使用概念验证原型的初步研究证明了这种方法的机械可行性。在这里，我们建议制造临床前级设备的原型，并表征该仪器在体外和体内的性能。完成该项目后，我们希望生成用于制造适合在人体安全试验中测试的临床级原型的仪器设计。