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
项目成果
期刊论文数量(0)
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科研奖励数量(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:
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:
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:
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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