Interstitial Chemophototherapy with Light-Activated Nanoparticulate Doxorubicin
光激活纳米颗粒阿霉素间质化学光疗
基本信息
- 批准号:10010747
- 负责人:
- 金额:$ 39.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-06 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdverse eventAnimalsBenchmarkingBiotechnologyBlood CirculationBlood VesselsBuffaloesCancer PatientClinicClinical ResearchCombination Drug TherapyComprehensive Cancer CenterComputer ModelsDataDoseDoxorubicinDrug Delivery SystemsDrug KineticsDrug vehicleEffectivenessElementsEncapsulatedFormulationGoalsHalf-LifeHepG2HourHumanIn VitroLasersLicensingLightLightingLiposomesLiver neoplasmsMagnetic Resonance ImagingMalignant NeoplasmsMalignant neoplasm of liverMethodsModelingMusNanotechnologyNational Cancer InstituteNeckOryctolagus cuniculusPUVA PhotochemotherapyPatientsPharmaceutical PreparationsPharmacologyPhasePhospholipidsPhototherapyPorphyrinsPre-Clinical ModelPrimary NeoplasmPrimary carcinoma of the liver cellsPropertyRattusRodentRoswell Park Cancer InstituteSafetySerumSmall Business Technology Transfer ResearchSurvival RateSystemTestingTherapeuticToxic effectTranslatingUltrasonographyWoodchuckanti-cancerbaseclinically relevantcommercializationdosimetryeffective therapyhepatic necrosisimage guidedimprovedin vivointerstitiallight dosimetrynanoparticulatenoveloutcome forecastphase 2 studypreclinical studyprimary endpointresponsesafety testingsecondary endpointsubcutaneoussuccesstreatment planningtumortumor ablationtumor growth
项目摘要
SUMMARY
Our goal is to advance the commercialization of interstitial chemo-phototherapy (I-CPT) as a potent antitumor
therapeutic option for locally advanced tumors. This application will focus on providing a proof of concept for
the benefit of I-CPT in the treatment locally advanced hepatocellular carcinoma (HCC). Patients with
inoperable locally advanced HCC have a poor prognosis with a 5-year survival rate of just 31%. The
combination of chemotherapy and phototherapy (CPT) involves administering a single agent such as
PhotoDox, a novel long-circulating, doxorubicin in porphyrin-phospholipid liposome formulation. The major
advantages of PhotoDox are: 1) it is thermally independent; 2) has rapid drug release upon 665-nm light
administration; 3) is long-circulating (~22 hour half-life), serum stable, and otherwise like DOXIL®; and 4) has
been demonstrated to be effective in multiple tumor models. PhotoDox was tested by the National Cancer
Institute Nanotechnology Characterization Lab, and was found to be similar to DOXIL® in in vitro toxicity and in
vivo pharmacokinetic studies.
POP Biotechnologies, Inc. has an exclusive license for PhotoDox. Dr. Shafirstein's team at Roswell Park
Cancer Institute (RPCI) has developed and validated a novel system to provide specific light dosimetry in
large tumors. In this STTR application, POP Biotechnologies will combine PhotoDox with Dr. Shafirstein’s
treatment planning approach to optimize and guide I-CPT for effective therapy of locally advanced liver tumors
by accomplishing the following aims:
Aim 1: To define light irradiance and fluence for effective I-CPT in subcutaneous HepG2 tumors.
The PI validated finite element method approach will be used to guide a light dose finding study to define a
safe and effective intratumoral light irradiance and fluence for I-CPT with PhotoDox. We will address the key
question: What is the optimal intratumoral light irradiance and fluence for I-CPT with PhotoDox?
Aim 2: Demonstrate the effectiveness of I-CPT in an orthotopic liver cancer rat model.
We will use the FEM to translate the optimal interstitial light delivery determined in murine tumors (Aim 1) to
larger orthotopic liver cancer in rats. We will address the key question: Can we deliver an effective I-CPT with
PhotoDox to an orthotopic model of liver tumor?
This translational Phase I project will provide required data to guide a Phase II study where our teams will test
and study I-CPT with PhotoDox in a spontaneous woodchuck HCC (available at RPCI) that is relevant to
understanding I-CPT treatment in the context of human liver cancer patients. If successful, I-CPT with
PhotoDox stands to benefit the majority of new liver cancer patients, who have inoperable and problematic
primary tumors.
总结
我们的目标是推进间质化学光疗(I-CPT)作为一种有效的抗肿瘤药物的商业化
局部晚期肿瘤的治疗选择。此应用程序将侧重于为以下方面提供概念验证:
I-CPT治疗局部晚期肝细胞癌(HCC)的疗效。患者
不能手术局部晚期HCC预后差,5年生存率仅为31%。的
化疗和光疗的组合(CPT)涉及施用单一药剂,
PhotoDox,一种新型的长循环阿霉素卟啉-磷脂脂质体制剂。主要
PhotoDox的优点是:1)它是热不依赖的; 2)在665-nm光下具有快速药物释放
施用; 3)是长循环的(~22小时半衰期),血清稳定的,并且在其他方面像DOXIL®;和4)具有
已被证明在多种肿瘤模型中有效。PhotoDox是由国家癌症中心测试的。
研究所纳米技术表征实验室,并被发现在体外毒性和免疫反应中与DOXIL®相似。
体内药代动力学研究。
POP Biotechnologies,Inc.拥有PhotoDox的独家授权罗斯威尔公园的沙菲尔斯坦医生的团队
癌症研究所(RPCI)已经开发并验证了一种新的系统,以提供特定的光剂量测定,
大肿瘤在这项STTR应用中,POP Biotechnologies将联合收割机PhotoDox与Shafirstein博士的
优化和指导I-CPT有效治疗局部晚期肝肿瘤的治疗计划方法
通过实现以下目标:
目的1:确定I-CPT在皮下HepG 2肿瘤中有效的光辐照度和能量密度。
PI确认的有限元方法将用于指导光剂量探索研究,以定义
安全有效的肿瘤内光辐照度和能量密度,用于I-CPT和PhotoDox。我们将解决关键问题
问:I-CPT联合PhotoDox的最佳肿瘤内光照度和能量密度是多少?
目的2:观察I-CPT对大鼠原位肝癌模型的治疗作用。
我们将使用FEM将在鼠肿瘤中确定的最佳间质光递送(Aim 1)转化为
大鼠的较大原位肝癌。我们将解决关键问题:我们能否提供有效的I-CPT,
PhotoDox用于原位肝肿瘤模型?
该翻译第一阶段项目将提供所需的数据,以指导我们的团队将测试的第二阶段研究
和研究I-CPT与PhotoDox在一个自发性土拨鼠HCC(可在RPCI),这是相关的
了解I-CPT治疗人类肝癌患者的背景。如果成功,I-CPT与
PhotoDox将使大多数新的肝癌患者受益,这些患者无法手术,
原发性肿瘤
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(0)
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GAL SHAFIRSTEIN其他文献
GAL SHAFIRSTEIN的其他文献
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{{ truncateString('GAL SHAFIRSTEIN', 18)}}的其他基金
Optical Surface Applicator Light Dosimetry for Ruthenium-based Photosensitizer Mediated Intraoperative Photodynamic Therapy
用于钌基光敏剂介导的术中光动力治疗的光学表面照射器光剂量测定
- 批准号:
10303270 - 财政年份:2021
- 资助金额:
$ 39.99万 - 项目类别:
Optical Surface Applicator Light Dosimetry for Ruthenium-based Photosensitizer Mediated Intraoperative Photodynamic Therapy
用于钌基光敏剂介导的术中光动力治疗的光学表面照射器光剂量测定
- 批准号:
10454364 - 财政年份:2021
- 资助金额:
$ 39.99万 - 项目类别:
Interstitial Chemophototherapy with Light-Activated Nanoparticulate Doxorubicin
光激活纳米颗粒阿霉素间质化学光疗
- 批准号:
10700814 - 财政年份:2020
- 资助金额:
$ 39.99万 - 项目类别:
Interstitial Chemophototherapy with Light-Activated Nanoparticulate Doxorubicin
光激活纳米颗粒阿霉素间质化学光疗
- 批准号:
10384796 - 财政年份:2020
- 资助金额:
$ 39.99万 - 项目类别:
Integrated Image-Guided Dosimetry and Treatment Planning for Photodynamic Therapy
光动力治疗的集成图像引导剂量测定和治疗计划
- 批准号:
9187830 - 财政年份:2015
- 资助金额:
$ 39.99万 - 项目类别:
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