Deploying Histotripsy Based Tumor Ablation Strategies to Treat Pancreatic Cancer
部署基于组织解剖学的肿瘤消融策略来治疗胰腺癌
基本信息
- 批准号:10612053
- 负责人:
- 金额:$ 45.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:AblationAcousticsAftercareAnatomyAnimal ModelAntitumor ResponseBlood VesselsCancer cell lineCessation of lifeChemotherapy and/or radiationClinicalClinical TrialsComplicationDataDevelopmentDiagnosisDiameterDiseaseDoseDuct (organ) structureElectroporationFamily suidaeFeedbackFocused Ultrasound TherapyFutureHumanImmune responseImmunocompetentImmunocompromised HostIn SituInjuryIntestinesLocationMalignant NeoplasmsMalignant neoplasm of pancreasMechanicsMethodsModalityModelingMusNodulePancreasPancreatic ductPancreatitisPatientsPhysiologicalPre-Clinical ModelPrognosisPulse PressureRecurrenceResearchRiskRuptureSafetyShapesSiteStenosisStructureSurvival RateTechniquesTestingTherapeuticTimeTissuesTransducersTreatment ProtocolsUnited StatesUnresectableWorkanti-tumor immune responsebile ductclinical translationclinically relevanteffective therapyfightingimage guidedimprovedin vivoinstrumentionizationmillimetermouse modelnovelnovel therapeutic interventionpancreatic cancer cellspancreatic cancer modelpancreatic cancer patientspancreatic neoplasmpatient derived xenograft modelphysical propertyporcine modelpre-clinicalpreservationpreventreal-time imagesresponsetranslation to humanstreatment strategytumortumor ablationtumor progressiontumor xenograft
项目摘要
PROJECT SUMMARY: Pancreatic cancer accounts for approximately 3% of all cancers in the United States
and approximately 7% of all cancer related deaths. New treatment paradigms are direly needed. Emerging tumor
ablation techniques have shown significant promise in both clinical and pre-clinical cancer studies. This proposal
will focus on histotripsy, which is the first non-invasive, non-ionizing, non-thermal, image-guided tumor ablation
modality that destroys tumors through the precise control of acoustic cavitation and is capable of overcoming
many of the limitations of the other tumor ablation modalities currently under development for this malignancy.
Recently, our research team completed proof-of-concept studies demonstrating that histotripsy is effective at
targeting the pancreas and produces consistent, fast, and complete ablations, even in proximity to critical
structures. Intriguingly, work by our team and others has also shown that histotripsy is effective in inducing
systemic anti-tumor responses, resulting in post-treatment tumor regression both locally and at metastatic sites.
However, the exact mechanism and level of control of this phenomenon is still unclear. The objective of this
proposal is to utilize our pre-clinical mouse and novel pig animal models to expand upon the preliminary data
presented in this proposal to generate critical mechanistic, safety, and efficacy data necessary to support future
clinical trials in pancreatic cancer patients. Our overarching hypothesis is that histotripsy can achieve safe and
selective focal ablation of pancreatic tumors and improve systemic anti-tumor immune responses. SPECIFIC
AIM 1: Determine histotripsy treatment parameters for precise and complete pancreatic tumor ablation.
Our preliminary data demonstrates the general feasibility of histotripsy ablation in the pancreas. This Aim will
test the hypothesis that histotripsy can achieve precise, efficient, and complete ablation of pancreatic tumors
without injuring critical structures, such as major blood vessels, bile ducts, and intestines. SPECIFIC AIM 2:
Establish histotripsy treatment strategies for pancreatic cancer that optimize tumor ablation and
systemic anti-tumor immune responses. This Aim will test the hypothesis that histotripsy is an effective
treatment modality for precise and complete pancreatic tumor ablation in vivo. We also postulate that due to the
unique features of histotripsy, focal tumor ablation results in predictable and tunable systemic anti-tumor host
immune responses reducing metastatic burden and preventing recurrence. SPECIFIC AIM 3: Define histotripsy
treatment parameters and determine its safety profile utilizing physiologically and clinically relevant
porcine models of pancreatic cancer. Pigs better mimic human patients in terms of anatomy, size, and
instrument scale. This Aim will test the hypothesis that histotripsy parameters can be established to effectively
ablate orthotopic pancreatic tumors under physiologically and clinically relevant in situ conditions.
SIGNIFICANCE: The studies outlined in this proposal will demonstrate the safety and efficacy of histotripsy for
pancreatic cancer ablation and will provide critical data necessary for clinical translation to human patients.
项目摘要:胰腺癌约占美国所有癌症的3%
大约有7%的与癌症相关的死亡。需要新的治疗范例。新兴肿瘤
消融技术在临床和临床前癌症研究中都表现出了巨大的希望。这个建议
将专注于组织肌肉,这是第一个非侵入性,非电离,非热,图像引导的肿瘤消融
通过精确控制声气水破坏肿瘤的方式,能够克服
目前正在开发这种恶性肿瘤的其他肿瘤消融方式的许多局限性。
最近,我们的研究团队完成了概念证明研究,表明Histotipsy在
靶向胰腺并产生一致,快速和完整的消融,即使靠近关键
结构。有趣的是,我们的团队和其他人的工作也表明,Histotipsy有效诱导
全身性抗肿瘤反应,导致治疗后肿瘤回归局部和转移性部位。
但是,这种现象的确切机制和控制水平仍不清楚。这个目的
建议是利用我们的临床前小鼠和新型猪动物模型来扩展初步数据
在此提案中提出的,以生成支持未来所必需的关键机理,安全性和功效数据
胰腺癌患者的临床试验。我们的总体假设是,组织疗法可以实现安全和
胰腺肿瘤的选择性局灶性消融并改善全身性抗肿瘤免疫反应。具体的
AIM 1:确定组织疗法治疗参数,以精确和完整的胰腺肿瘤消融。
我们的初步数据证明了胰腺中组织疗法消融的一般可行性。这个目标
测试组织疗法可以实现胰腺肿瘤的精确,有效和完整消融的假设
没有伤害临界结构,例如主要的血管,胆管和肠道。具体目标2:
建立胰腺癌的组织疗法治疗策略,以优化肿瘤消融和
全身性抗肿瘤免疫反应。这个目标将检验组织疗法是有效的假设
在体内进行精确和完整的胰腺肿瘤消融的治疗方式。我们还推测,由于
组织肌肉,局灶性肿瘤消融的独特特征会导致可预测且可调的全身性抗肿瘤宿主
免疫反应减轻转移负担并预防复发。特定目标3:定义组织疗法
治疗参数并确定其安全性利用生理和临床相关的安全性
胰腺癌的猪模型。猪就解剖学,大小和
仪表尺度。该目标将检验以下假设,即可以建立组织摄氏参数以有效地建立
在生理和临床上相关的原位条件下,在生理和临床上植入原位胰腺肿瘤。
意义:该提案中概述的研究将证明组织疗法的安全性和功效
胰腺癌消融,将提供对人类患者临床翻译所需的重要数据。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study.
- DOI:10.3390/pharmaceutics15061585
- 发表时间:2023-05-24
- 期刊:
- 影响因子:5.4
- 作者:Imran KM;Tintera B;Morrison HA;Tupik JD;Nagai-Singer MA;Ivester H;Council-Troche M;Edwards M;Coutermarsh-Ott S;Byron C;Clark-Deener S;Uh K;Lee K;Boulos P;Rowe C;Coviello C;Allen IC
- 通讯作者:Allen IC
NLRX1 functions as a tumor suppressor in Pan02 pancreatic cancer cells.
- DOI:10.3389/fonc.2023.1155831
- 发表时间:2023
- 期刊:
- 影响因子:4.7
- 作者:
- 通讯作者:
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Irving C Allen其他文献
Irving C Allen的其他文献
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{{ truncateString('Irving C Allen', 18)}}的其他基金
Optimization of High Frequency Irreversible Electroporation (H-FIRE) for tumor ablation and immune system activation in pancreatic cancer applications
高频不可逆电穿孔 (H-FIRE) 的优化,用于胰腺癌应用中的肿瘤消融和免疫系统激活
- 批准号:
10659581 - 财政年份:2023
- 资助金额:
$ 45.71万 - 项目类别:
Deploying Histotripsy Based Tumor Ablation Strategies to Treat Pancreatic Cancer
部署基于组织解剖学的肿瘤消融策略来治疗胰腺癌
- 批准号:
10418848 - 财政年份:2022
- 资助金额:
$ 45.71万 - 项目类别:
Employing Novel Porcine Models of Orthotopic Pancreatic Cancer to Evaluate Histotripsy Based Tumor Ablation Strategies
采用新型猪原位胰腺癌模型来评估基于组织解剖的肿瘤消融策略
- 批准号:
9807506 - 财政年份:2019
- 资助金额:
$ 45.71万 - 项目类别:
Evaluating NLR Modulation of Canonical and Non-Canonical NF-kB Signaling in IBD
评估 IBD 中规范和非规范 NF-kB 信号传导的 NLR 调制
- 批准号:
8943147 - 财政年份:2015
- 资助金额:
$ 45.71万 - 项目类别:
NLR Regulation of Gastrointestinal Inflammation and Tumorigenesis
NLR 对胃肠道炎症和肿瘤发生的调节
- 批准号:
8468173 - 财政年份:2011
- 资助金额:
$ 45.71万 - 项目类别:
NLR Regulation of Gastrointestinal Inflammation and Tumorigenesis
NLR 对胃肠道炎症和肿瘤发生的调节
- 批准号:
8165280 - 财政年份:2011
- 资助金额:
$ 45.71万 - 项目类别:
NLR Regulation of Gastrointestinal Inflammation and Tumorigenesis
NLR 对胃肠道炎症和肿瘤发生的调节
- 批准号:
8731867 - 财政年份:2011
- 资助金额:
$ 45.71万 - 项目类别:
NLR Regulation of Gastrointestinal Inflammation and Tumorigenesis
NLR 对胃肠道炎症和肿瘤发生的调节
- 批准号:
8572668 - 财政年份:2011
- 资助金额:
$ 45.71万 - 项目类别:
NLR Regulation of Gastrointestinal Inflammation and Tumorigenesis
NLR 对胃肠道炎症和肿瘤发生的调节
- 批准号:
8331448 - 财政年份:2011
- 资助金额:
$ 45.71万 - 项目类别:
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