Parametric optimization of ultrasound-mediated immuno-modulation for pancreatic cancer therapy
超声介导的胰腺癌免疫调节的参数优化
基本信息
- 批准号:10092130
- 负责人:
- 金额:$ 10.82万
- 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:2020-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAcousticsAgitationAntibodiesAntigen PresentationAntigensB-LymphocytesBiologicalBlood VesselsCD8-Positive T-LymphocytesCellsClinicClinicalCoagulative necrosisCombination immunotherapyCommunitiesCytometryDataDendritic CellsDiagnosisDiagnostic ImagingDiagnostic testsDiseaseDistant MetastasisEffectivenessExcisionFDA approvedFibroid TumorFocused UltrasoundFocused Ultrasound TherapyGoldHistologyHyperthermiaImageImmuneImmune checkpoint inhibitorImmune responseImmunizationImmunologic MarkersImmunologicsImmunophenotypingImmunosuppressionImmunotherapeutic agentImmunotherapyIncidenceInfiltrationInfrastructureInnovative TherapyInvestigationKnowledgeMalignant NeoplasmsMalignant neoplasm of pancreasMeasuresMechanicsMediatingMethodsMicrobubblesMicroscopicMotivationMusMyeloid CellsNatureNeoplasm MetastasisOperative Surgical ProceduresPancreatic AdenocarcinomaPancreatic Ductal AdenocarcinomaPatientsPrimary NeoplasmPublic HealthPublishingRadiationRadiation therapyRecurrenceResearchResectableResistanceRoleSignal TransductionSurvival RateSystemT-Cell ProliferationT-LymphocyteTechnologyTestingTherapeuticTherapeutic EffectTimeTissuesTranslationsTreatment EfficacyTreatment ProtocolsTumor BurdenTumor-infiltrating immune cellsUltrasonographyUnited StatesUterine FibroidsVariantVascular PermeabilitiesWorkXenobioticsalternative treatmentanti-CTLA4anti-CTLA4 antibodiesanti-PD-1anti-PD1 therapyanti-tumor immune responsebasecancer therapycancer typechemotherapeutic agentclinical translationdesigneffective therapyeffector T cellexperiencehigh resolution imagingimage guidedimaging modalityimmune checkpoint blockadeimmune healthimmunogenicimmunoregulationimprovedinsightintraperitonealmouse modelmultiplex assayneoplastic cellnew technologynovelnovel strategiesnovel therapeuticspancreatic cancer modelpancreatic cancer patientspancreatic ductal adenocarcinoma modelpancreatic neoplasmpre-clinicalpre-clinical researchpreclinical studypreventresponseside effectskin damagesoundstandard of caretraffickingtumortumor microenvironmenttumor-immune system interactions
项目摘要
PROJECT SUMMARY
The immunosuppressive tumor microenvironment creates a formidable challenge to treatment of pancreatic
ductal adenocarcinoma (PDAC). Its resistance to the “gold standard” chemo- and radiation therapy and to
immune checkpoint blockade, which has recently been FDA approved for other cancer types, is motivation for
to develop new therapies for treating PDAC. Poor responses to therapy are thought to be due to paucity of
intratumoral effector T cells, which correlates with profound immunosuppression, insufficient antigen
presentation as well as desmoplasia-driven compression of tumor vasculature. Recently, non-invasive focused
ultrasound (FUS) has emerged as an immunomodulatory cancer therapy, with several studies showing primary
and metastatic tumor burden reduction after ultrasound treatment. However, lack of knowledge regarding
mechanisms of action with this very new technology as well as optimal ultrasound parameters to achieve
consistently effective immunotherapy improvement presents a barrier to clinical or even widespread preclinical
use. Furthermore, technical difficulties associated with imaging and consequently, precise treatment of
pancreatic tumors with ultrasound, have complicated preclinical studies. Here, we propose a rigorous study of
immunological biomarker changes in response to varying focused ultrasound parameters to both elucidate
optimal ultrasound parameters as well as mechanism. Therapeutic ultrasound will be varied across ablative, mild
hyperthermia, low-intensity radiation force, and cavitation regimes, with and without microbubbles. Our proposed
research will use clinically meaningful orthotopic murine models of pancreatic cancer as well as multiplex mass
cytometry-based immuno-phenotyping. Furthermore, we will use novel real-time high-resolution image-guided
therapeutic FUS technology to enable precise image guided treatment. Once we have evaluated promising
acoustic parameters, we will test the treatment protocols with immune checkpoint blockade to evaluate increase
in therapeutic efficacy. This effort will inform the optimal design of combined ultrasound-immunotherapy
strategies against PDAC.
项目总结
免疫抑制的肿瘤微环境给胰腺的治疗带来了巨大的挑战。
导管腺癌(PDAC)。它对“黄金标准”化疗和放射治疗的抵抗力
免疫检查点阻断,最近已被FDA批准用于其他癌症类型,是推动
开发治疗PDAC的新疗法。对治疗的不良反应被认为是由于缺乏
与深度免疫抑制相关的瘤内效应性T细胞,抗原不足
肿瘤血管的表现以及促结缔组织增生性压迫。最近,无创聚焦
超声(FUS)已成为一种免疫调节性癌症治疗方法,多项研究表明
超声治疗后转移瘤负担减轻。然而,缺乏关于以下方面的知识
这项非常新的技术的作用机理以及实现最佳超声参数
持续有效的免疫疗法的进步对临床甚至临床前的广泛应用构成了障碍。
使用。此外,与成像相关的技术困难,以及由此导致的精确治疗
胰腺肿瘤与超声相比,有复杂的临床前研究。在这里,我们建议对
免疫生物标记物对不同聚焦超声参数反应的变化
最佳的超声参数以及机理。治疗性超声将在消融性的、温和的
热疗、低强度辐射力和空化制度,有和没有微泡。我们的建议
研究将使用具有临床意义的原位胰腺癌小鼠模型以及多个肿块
基于细胞学的免疫表型分析。此外,我们还将使用新颖的实时高分辨率图像制导
治疗性FUS技术,实现精确的图像引导治疗。一旦我们评估了前景
声学参数,我们将测试治疗方案与免疫检查点阻断,以评估增加
在治疗效果上。这一努力将为超声-免疫联合治疗的最佳设计提供信息。
针对PDAC的战略。
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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Paul A Dayton其他文献
Therapeutic ultrasound as a potential male contraceptive: power, frequency and temperature required to deplete rat testes of meiotic cells and epididymides of sperm determined using a commercially available system
- DOI:
10.1186/1477-7827-10-7 - 发表时间:
2012-01-01 - 期刊:
- 影响因子:4.700
- 作者:
James K Tsuruta;Paul A Dayton;Caterina M Gallippi;Michael G O'Rand;Michael A Streicker;Ryan C Gessner;Thomas S Gregory;Erick JR Silva;Katherine G Hamil;Glenda J Moser;David C Sokal - 通讯作者:
David C Sokal
Paul A Dayton的其他文献
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{{ truncateString('Paul A Dayton', 18)}}的其他基金
Parametric optimization of ultrasound-mediated immuno-modulation for pancreatic cancer therapy
超声介导的胰腺癌免疫调节的参数优化
- 批准号:
9979314 - 财政年份:2020
- 资助金额:
$ 10.82万 - 项目类别:
Parametric optimization of ultrasound-mediated immuno-modulation for pancreatic cancer therapy
超声介导的胰腺癌免疫调节的参数优化
- 批准号:
10375345 - 财政年份:2020
- 资助金额:
$ 10.82万 - 项目类别:
Treating Tumoral Hypoxia via Ultrasound-Guided Oxygen Release for Improving Radiation Therapy
通过超声引导释氧治疗肿瘤缺氧以改善放射治疗
- 批准号:
9978579 - 财政年份:2018
- 资助金额:
$ 10.82万 - 项目类别:
Treating Tumoral Hypoxia via Ultrasound-Guided Oxygen Release for Improving Radiation Therapy
通过超声引导释氧治疗肿瘤缺氧以改善放射治疗
- 批准号:
10402933 - 财政年份:2018
- 资助金额:
$ 10.82万 - 项目类别:
Treating Tumoral Hypoxia via Ultrasound-Guided Oxygen Release for Improving Radiation Therapy
通过超声引导释氧治疗肿瘤缺氧以改善放射治疗
- 批准号:
10632112 - 财政年份:2018
- 资助金额:
$ 10.82万 - 项目类别:
Treating Tumoral Hypoxia via Ultrasound-Guided Oxygen Release for Improving Radiation Therapy
通过超声引导释氧治疗肿瘤缺氧以改善放射治疗
- 批准号:
10163814 - 财政年份:2018
- 资助金额:
$ 10.82万 - 项目类别:
Acoustic Angiography Using Dual-Frequency and Ultrawideband CMUT Arrays
使用双频和超宽带 CMUT 阵列的声学血管造影
- 批准号:
9899252 - 财政年份:2018
- 资助金额:
$ 10.82万 - 项目类别:
High Frame Rate 3-D Super Resolution Ultrasound Microvascular Imaging
高帧率 3D 超分辨率超声微血管成像
- 批准号:
10478978 - 财政年份:2017
- 资助金额:
$ 10.82万 - 项目类别:
High Frame Rate 3-D Super Resolution Ultrasound Microvascular Imaging
高帧率 3D 超分辨率超声微血管成像
- 批准号:
10249991 - 财政年份:2017
- 资助金额:
$ 10.82万 - 项目类别:
High Frame Rate 3-D Super Resolution Ultrasound Microvascular Imaging
高帧率 3D 超分辨率超声微血管成像
- 批准号:
9393119 - 财政年份:2017
- 资助金额:
$ 10.82万 - 项目类别:
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