BIOTHERAPY OF BRAIN TUMORS BY RADIOIODINATED SAPC-DOPS NANOVESICLES

放射性碘化 SAPC-DOPS 纳米囊泡对脑肿瘤的生物治疗

• 批准号: 9578288
• 负责人: Brian D. Gray
• 金额: $ 30万
• 依托单位: MOLECULAR TARGETING TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-18 至 2018-06-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9578288
• 关键词: Address; Back; Biological Response Modifier Therapy; Blood; Brain Neoplasms; Coupled; Data; Drug Delivery Systems; Exhibits; Glioblastoma; Goals; Label; Lead; Lipid Binding; Lipids; Malignant Neoplasms; Malignant neoplasm of brain; Modeling; Orphan Drugs; Phase I Clinical Trials; Phosphatidylserines; Property; Publishing; Radiation; Radiation exposure; Radiation therapy; Radiolabeled; Radionuclide therapy; Reporter; Research Proposals; System; Testing; Therapeutic; Tumor Markers; beta-Glucosidase Stimulating Protein; cancer cell; chemotherapy; extracellular; lipophilicity; mouse model; nanovesicle; neoplastic cell; novel; pre-clinical; tumor

There is an urgent need for more effective drug delivery agents for treatment of brain tumors, which are among the most aggressive and intractable cancers. SapC-DOPS, a nanovesicle composed of saposin C (SapC) coupled to dioleoylphosphatidylserine (DOPS), has proven tumor targeting properties, which include crossing the blood-brain tumor barrier and binding the lipid tumor marker, extracellular phosphatidylserine (PS). It also exhibits antitumor activities in preclinical glioblastoma (GBM) models. We hypothesize that endowing SapC-DOPS nanovesicles with a radiolabeled lipophilic reporter will create a novel agent with superior efficacy for targeted radionuclide therapy (TRT) of GBMs. Treatment options for GBMs are very limited, and standard therapies with radiation and/or chemotherapy provide only modest survival benefits with potential deleterious effects. To address these issues, we propose to create a novel cancer-selective, targeted radiolabeled SapC-DOPS for TRT of GBMs. A unique advantage of MTTI's approach lies in the feedforward therapeutic mechanism of the novel compound: radiation exposure is known to increase PS externalization in tumor cells, thus leading to enhanced anticancer effects by PS-targeted SapC-DOPS nanovesicles. This proposal is backed by extensive, published and unpublished, preliminary data, the FDA Orphan Drug designation of SapC-DOPS, and an ongoing clinical phase I trial.

脑肿瘤是最具侵袭性和难治性的癌症之一，迫切需要更有效的药物递送剂来治疗脑肿瘤。皂苷C- dops是一种由皂苷C组成的纳米囊泡