In-Situ Gelling Protein Polymer Intravascular Embolic Agent for Hepatic Carcinoma
原位胶凝蛋白聚合物血管内栓塞剂治疗肝癌
基本信息
- 批准号:9350251
- 负责人:
- 金额:$ 69.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-21 至 2019-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAnimalsArteriesBAY 54-9085Biological ProductsBiological Response Modifier TherapyBloodBlood TestsBlood flowCaliberCarcinomaCatheterizationCathetersCharacteristicsChemoembolizationChronicClinicalClinical TreatmentClinical TrialsCollectionDevelopment PlansDiseaseDisease ProgressionDoxorubicinDrug Delivery SystemsDrug FormulationsDrug KineticsEligibility DeterminationEndotoxinsEnsureEvaluationExcisionExcretory functionFamily suidaeFermentationFormulationGelGenetic EngineeringGoldGrantGuidelinesHealthHemolysisHepaticHepatic arteryHumanHydrogelsImplantIn SituIn VitroIncidenceInjectableInjection of therapeutic agentInterventional radiologyIntramuscularLaboratoriesLaboratory PersonnelLaboratory ProceduresLiquid substanceLiverLiver neoplasmsLungMagnetic Resonance ImagingMalignant NeoplasmsMalignant neoplasm of liverMetabolismMethodsMicrofluidic MicrochipsModelingMolecular WeightOperative Surgical ProceduresOryctolagus cuniculusPatientsPerformancePharmaceutical PreparationsPhasePolymersPreparationPrimary carcinoma of the liver cellsProceduresProductionPropertyProtein EngineeringProteinsRattusReactionResearchSafetySilkSmall Business Technology Transfer ResearchSolidSourceSterilizationStructureSurvival RateSymptomsSyringesSystemTechniquesTestingTherapeuticTherapeutic EmbolizationTimeTissuesToxic effectToxicity TestsToxicologyTreatment EfficacyUrineVenous systemViscosityWorkanalytical methodaqueousbasebiomaterial compatibilitybioresorptioncancer cellcancer imagingchemotherapeutic agentchemotherapycomparative efficacycontrolled releasedesigndrug distributionimmunoreactivityimplantable deviceimplantationimprovedin vivokillingsliver functionliver transplantationmethod developmentnanoparticulatenovelpatient populationperformance testspre-clinicalscale upstandard carestandard of caresystemic toxicitytumortumor vascular supply
项目摘要
SUMMARY
This STTR Phase II proposal addresses the significant need for improved treatment options for patients with
liver cancer, the fifth highest incidence of cancer in the world. Because of the lack of symptoms, hepatocellular
carcinoma (HCC) is detected at advanced stages in 84% of cases, for which the 1-year survival rate is 22% and
at 5 years it is 5%. The only curative option for advanced HCC is surgical liver resection and liver transplantation,
unfortunately not available to most patients due to the lack of donor livers and the rapid progression of the
disease. As HCC is generally unresponsive to systemic chemotherapy, transcatheter arterial
chemoemobolization (TACE) is the most widely used, localized treatment that can slow the progression of the
disease. Current embolizing agents are deficient in precision of catheter delivery or compatibility for effective
delivery of chemotherapeutic agents, especially high-molecular weight biotherapeutics. The objective of the
proposed work is to characterize the novel liquid embolizing agent composed of the genetically engineered
protein polymer, SELP (silk-elastinlike protein)-815K, which based on our previous work has demonstrated
properties uniquely suited for this application. Unlike existing agents, SELP-815K will be injectable as a liquid,
able to penetrate into the tumor arteries, and transform to an insoluble hydrogel in-situ forming a substantially
durable occlusion. The embolizing liquid will be completely aqueous and compatible with drugs and new
biotherapeutics, enabling their localized controlled release. The protein-based SELP-815K will eventually
biodegrade, enabling subsequent TACE treatments. SELP-815K liquid embolic will enable the controlled delivery
of chemotherapeutic drugs and new biotherapeutic agents with increased precision of transcatheter delivery for
more selective embolization, reduced off-target toxicity, and reduced collateral damage to the healthy liver.
Consequently, TACE treatment will be offered to a larger patient population having a greater number of tumors
and/or greater tumor size.
The aims of the research are: (1) to characterize the delivery of single and multiple drugs via the SELP-815K
gel network; (2) to conduct in vivo studies in the McA-RH7777 HCC liver tumor rat model to evaluate therapeutic
performance; (3) to conduct SELP-815K manufacturing and analytical methods development; and (4) to conduct
GLP preclinical toxicology and performance testing of manufactured SELP-815K embolic.
概括
该STTR II期提案解决了改善治疗方案的重要需求
肝癌,世界上癌症的第五大发病率。由于缺乏症状,肝细胞
在84%的病例中,在高级阶段中检测到癌(HCC),其生存率为22%,并且
在5年的时间为5%。晚期HCC的唯一治愈方法是手术肝切除和肝移植,
不幸的是,由于缺乏供体肝和大多数患者的迅速发展,大多数患者无法获得
疾病。由于HCC通常对全身化疗无反应,因此经导管动脉
化学杂种化(TACE)是最常用,最广泛的局部治疗方法,可以减慢
疾病。当前的栓塞剂缺乏导管递送的精度或有效的兼容性
化学治疗剂的递送,尤其是高分子重量生物治疗剂。目的
建议的工作是表征由基因工程组成的新型液体栓塞剂
蛋白质聚合物,SELP(丝绸丙酯蛋白)-815K,基于我们以前的工作已证明
属性非常适合此应用程序。与现有代理不同,SELP-815K将作为液体注射,
能够渗透到肿瘤动脉中,并转化为基本形成的原位的不溶性水凝胶
耐用的阻塞。栓塞液体将完全是水性的,并且与药物和新的液体兼容
生物治疗学,使其局部受控释放。基于蛋白质的SELP-815K最终将
生物降解,从而实现随后的TACE治疗。 SELP-815K液体栓塞将实现受控的输送
化学治疗药物和新的生物治疗剂的经导管递送精度提高
更有选择性的栓塞,降低了脱靶毒性,并减少了对健康肝脏的附带损害。
因此,将向具有更多肿瘤数量的较大患者群体提供TACE治疗
和/或更大的肿瘤大小。
该研究的目的是:(1)通过SELP-815K表征单一药物和多种药物
凝胶网络; (2)在MCA-RH7777 HCC肝肿瘤大鼠模型中进行体内研究以评估治疗
表现; (3)进行SELP-815K制造和分析方法开发; (4)进行
GLP临床前毒理学和制造的SELP-815K栓塞性能测试。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(2)
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Darwin Leroy Cheney其他文献
Darwin Leroy Cheney的其他文献
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{{ truncateString('Darwin Leroy Cheney', 18)}}的其他基金
Recombinant Silk Elastin-like Protein Polymers for the Embolization of Cerebral Aneurysms
用于脑动脉瘤栓塞的重组丝弹性蛋白样蛋白聚合物
- 批准号:
9348145 - 财政年份:2017
- 资助金额:
$ 69.45万 - 项目类别:
Recombinant Silk Elastin-like Protein Polymers for the Embolization of Cerebral Aneurysms
用于脑动脉瘤栓塞的重组丝弹性蛋白样蛋白聚合物
- 批准号:
9542385 - 财政年份:2017
- 资助金额:
$ 69.45万 - 项目类别:
In-Situ Gelling Protein Polymer Intravascular Embolic Agent for Hepatic Carcinoma
原位胶凝蛋白聚合物血管内栓塞剂治疗肝癌
- 批准号:
9988599 - 财政年份:2012
- 资助金额:
$ 69.45万 - 项目类别:
In-Situ Gelling Protein Polymer Intravascular Embolic Agent for Hepatic Carcinoma
原位胶凝蛋白聚合物血管内栓塞剂治疗肝癌
- 批准号:
9202761 - 财政年份:2012
- 资助金额:
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Backbone Degradable Polymer-drug Conjugates for the Treatment of Ovarian Cancer
用于治疗卵巢癌的主链可降解聚合物-药物缀合物
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8124344 - 财政年份:2011
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