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.
项目概要
免疫抑制性肿瘤微环境给胰腺癌的治疗带来了巨大的挑战
导管腺癌(PDAC)。它对“金标准”化疗和放疗的抵抗力以及
免疫检查点阻断最近已被 FDA 批准用于其他癌症类型,这是
开发治疗 PDAC 的新疗法。对治疗的反应不佳被认为是由于缺乏
瘤内效应 T 细胞,与深度免疫抑制、抗原不足相关
呈现以及结缔组织增生驱动的肿瘤脉管系统压缩。最近,非侵入性的重点
超声(FUS)已成为一种免疫调节癌症疗法,多项研究表明原发性
超声治疗后转移性肿瘤负荷减少。然而,缺乏相关知识
这种新技术的作用机制以及最佳超声参数以实现
持续有效的免疫治疗改进对临床甚至广泛的临床前治疗构成了障碍
使用。此外,与成像相关的技术困难以及因此的精确治疗
胰腺肿瘤的超声检查,有复杂的临床前研究。在此,我们建议进行一项严格的研究
免疫生物标志物响应不同的聚焦超声参数而变化,以阐明
最佳超声参数和机制。超声治疗将根据消融性、轻度
热疗、低强度辐射力和空化状态,有或没有微泡。我们提出的
研究将使用具有临床意义的胰腺癌原位小鼠模型以及多重肿块
基于细胞计数的免疫表型分析。此外,我们将使用新颖的实时高分辨率图像引导
治疗性 FUS 技术可实现精确的图像引导治疗。一旦我们评估了有前途的
声学参数,我们将测试免疫检查点封锁的治疗方案以评估增加
在治疗功效上。这项工作将为联合超声免疫疗法的优化设计提供信息
针对 PDAC 的策略。
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:
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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