Novel Cell Delivery Method for Brain Tumor Therapy

用于脑肿瘤治疗的新型细胞递送方法

• 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
• 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

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）：即使采用目前的积极治疗方法，大多数原发性恶性脑肿瘤（胶质瘤）患者存活时间也不到两年。虽然靶向治疗正在开发中，但血脑屏障阻止大分子穿透中枢神经系统并进入大脑。由于胶质瘤很少转移，局部肿瘤治疗可能足以防止疾病进展。因此，研究人员正在开发方法，允许将肿瘤特异性大分子直接输送到脑肿瘤中。然而，这些方法需要注入大量的药物，这对于大脑等空间有限的器官来说既耗时又不切实际。因此，迫切需要改进将靶向大分子输送到脑肿瘤的方法。该项目的目标是制造和评估一种新型仪器的可行性，该仪器能够使用图像引导的微创技术在脑肿瘤中创建一个腔。由该仪器产生的空腔可以用作储存库，将抗癌大分子或细胞直接输送到肿瘤中。在图像引导下，仪器通过一个小的毛刺孔插入肿瘤，用于中心肿瘤的去膨胀。该器械独特的机械特性使其能够通过一个小通道分离、粉碎、烧灼和抽吸肿瘤组织。使用概念验证原型的初步研究已经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装置的原型，并表征该仪器在体外和体内的性能。在完成这个项目后，我们期望产生用于制造临床级原型的仪器设计，适合在人体安全试验中进行测试。